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On the Mechanisms of the Effects of Ionizing Radiation on Diblock and Random Copolymers of Poly(Lactic Acid) and Poly(Trimethylene Carbonate) Agnieszka Adamus-Wlodarczyk 1 , Radoslaw A. Wach 1, *, Piotr Ulanski 1 , Janusz M. Rosiak 1 , Marta Socka 2 , Zois Tsinas 3 and Mohamad Al-Sheikhly 3 1

2 3

*

Institute of Applied Radiation Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland; [email protected] (A.A.-W.); [email protected] (P.U.); [email protected] (J.M.R.) Department of Polymer Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland; [email protected] Department of Materials Science and Engineering, University of Maryland, 4418 Stadium Dr., College Park, MD 20742-2115, USA; [email protected] (Z.T.); [email protected] (M.A.-S.) Correspondence: [email protected]; Tel.: +48-42-631-3164

Received: 9 May 2018; Accepted: 11 June 2018; Published: 16 June 2018







Abstract: This article demonstrates that ionizing radiation induces simultaneous crosslinking and scission in poly(trimethylene carbonate-co-d-lactide) diblock and random copolymers. Copolymer films were electron-beam (EB) irradiated up to 300 kGy under anaerobic conditions and subsequently examined by evaluation of their structure (FT-IR, NMR), molecular weight, intrinsic viscosities, and thermal properties. Radiation chemistry of the copolymers is strongly influenced by the content of ester linkages of the lactide component. At low lactide content, crosslinking reaction is the dominant one; however, as the lactide ratio increases, the ester linkages scission becomes more competent and exceeds the crosslinking. Electron paramagnetic resonance (EPR) measurements indicate that higher content of amorphous carbonate units in copolymers leads to a reduction in free radical yield and faster radical decay as compared to lactide-rich compositions. The domination of scission of ester bonds was confirmed by identifying the radiolytically produced alkoxyl and acetyl radicals, the latter being more stable due to its conjugated structure. Keywords: electron beam irradiation; crosslinking; scission; PLA; PTMC; poly(trimethylene carbonate-co-d-lactide); diblock copolymers; random copolymers; EPR; alkoxyl radicals; acetyl radicals

1. Introduction Biodegradable polymers are excellent solutions for a wide range of applications, including those in biomedical and pharmaceutical fields. Among medical polymers, aliphatic polyesters of lactides and poly(trimethylene carbonate) (PTMC) have been extensively investigated due to their favorable properties, such as toxicological safety, controlled biodegradability and, if blended or copolymerized, tailorable mechanical properties [1–3]. Poly(lactic acid) (PLA) is a well-known typical biodegradable and biocompatible polymer, which is commonly produced from renewable resources [4]. This rigid polymer is utilized in load-bearing implantable medical devices and drug release matrices. It is investigated towards applications as disposable primary commodities or environmentally friendly packaging materials [5,6]. Biodegradation of lactides occurs through hydrolysis of ester linkages in the main chain, yielding naturally occurring lactic acid. Nevertheless, its poor thermal stability and deficient mechanical properties (high stiffness) limit the area of PLA application [7,8]. To improve heat stability and Polymers 2018, 10, 672; doi:10.3390/polym10060672

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mechanical properties, various methods such as annealing, adding nucleating agents, fillers in form of fibers or nanoparticles were applied [9–12]. Alternatively, specific chemical and physical treatments were also applied to introduce crosslinking between PLA macromolecules to alter disadvantageous properties [13–15]. Opposite to PLA, PTMC is a flexible, biodegradable, and biocompatible synthetic polymer, showing attractive surface erosion behavior in vivo. Compared to the relatively rigid polyesters based on glycolide or lactides, materials with lower modulus might have advantageous properties for medical applications in soft tissue engineering or drug delivery systems [16–18]. However, PTMC has not been widely used in medical applications, mainly because its unsatisfactory low tensile strength and creeping tendency that significantly limits its application for other uses. For this reason, TMC monomer is often used in copolymers with different lactones, for instance to manufacture surgical sutures, e.g., lactide [19], ε-caprolatone [20], glycolide [21]. Combination of the two components of different properties, the lactide and PTMC, results in a material more flexible than pure PLA, but with much improved mechanical properties as compared to PTMC. Therefore, introducing PTMC into PLA through copolymerization, i.e., synthesis of poly(lactic acid)-co-poly(trimethylene carbonate), becomes an important way to fine-tune important properties of PLA. Such copolymers may be utilized in variety of current and emerging applications, e.g., resorbable sutures, long or short term implantable devices, microparticles for drug delivery systems, bone graft substitutes, etc. [22–25]. Response of the organism to the implanted biodegradable material, besides its assumed biocompatibility, depends on numerous factors, such as place of implantation and the surrounding tissue, chemistry of the material, mechanical, morphological, and surface properties of the implant, mechanism, and kinetics of biodegradation along with metabolism or resorption of degradation products. One of the important issues in the manufacturing of medical devices is providing sterility. Several procedures can be employed for sterilization of PLA or PTMC polymers, such as sterilization with ethylene oxide gas [26], low-temperature plasma, injection molding process, steam [27,28]. On the other hand, radiation processing and the commercially dominating sterilization process by high-energy radiation have been reported for modification and sterilization of PLA [29–31] and poly(d-lactic acid) (PDLA)-based composite materials [32], yet with severe restrictions. Because of high efficiency, excellent penetration characteristics and financial benefits of using ionizing radiation, radiation sterilization technique is widely applicable and eliminates problems which may appear with other sterilization methods, such as for instance high temperature, penetration of ethylene oxide gas or hydrogen peroxide (for cold plasma sterilization method), toxic residuals and need for quarantine period, surface chemistry change, or non-uniformity of sterilization. Nevertheless, radiation sterilization of polymers may also be problematic due to the damaging effects of radiation on some polymeric materials. Radiation can modify the physical and chemical properties of polymers through main-chain scission and crosslinking. Upon irradiation, free radicals are formed randomly along polymer chains. They can react with each other or initiate other reactions, mainly chain scission (degradation). This in turn gives rise to changes in chemistry and material properties. A recombination of two macroradicals leads to crosslinking, which generally results in enhancement of physical properties, whereas degradation, manifesting itself by reduction in molecular weight, typically leads to detrimental changes of mechanical properties. In many polymers both processes take place simultaneously and the final results of irradiation depend on the ratio of their efficiencies, which can be quantified as radiation-chemical yields of intermolecular crosslinking and chain scission, thus chemical changes and yields should be always determined prior to further physical properties testing [33,34]. The behavior of both PLA and PTMC homopolymers under irradiation is relatively well known. Poly(lactic acid) has high mechanical strength, but in the pure form, without additives, it cannot be effectively modified or sterilized using ionizing radiation because it degrades readily while irradiated, leading subsequently to a polymer of lower molecular weight and lesser properties [35]. There are

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some reports concerning radiation-induced crosslinking of PLA using an added crosslinking agent, for instance triallyl isocyanurate, but the additive is biologically unsafe [35,36]. PTMC undergoes simultaneous degradation and cross-linking initiated by radiation, nevertheless the latter process predominates, which results in an increase in the molecular weight. Therefore, PTMC can be sterilized by radiation technique [37]. Although some data on the effects of electron-beam (EB) irradiation on PLA and its copolymers have been published [38–40], no studies have been reported so far regarding the effects of radiation on the properties of PLA-co-PTMC copolymers. In the present work, chemical changes occurring upon irradiation of diblock and random copolymers of various molar compositions were investigated. Molecular weight, intrinsic viscosity and thermal properties were examined as a function of electron beam irradiation. Subsequently, radiation chemical yields of chain scission and crosslinking in copolymers were evaluated, thus copolymers of compositions and microstructure that are prone to scission or crosslinking were identified. Yield and decay of radicals formed in irradiated systems were examined as a function of copolymer molecular structure by electron paramagnetic resonance spectroscopy (EPR). Ionizing radiation induces several reactions in polymers, of which those leading to main chain scission and to crosslinking of macromolecules are the most important from the point of view of polymer physical properties and of its suitability for particular applications. Scission of only a few bonds in the polymer backbone may cause tremendous alternation of mechanical properties due to reduction of polymer molecular weight. On the contrary, intermolecular crosslinking results in an increase of molecular weight of the polymer, therefore one may expect improvement of physical properties of the material. In some cases, when crosslinking predominates over degradation, a chemical (covalent) gel may be formed and the polymer becomes insoluble. It is anticipated that modification of physical and chemical properties may be accompanied by only minor changes in chemical composition of the polymers. 2. Materials and Methods 2.1. Materials and Polymers Synthesis Homopolymers of PTMC and PDLA were used as reference in physicochemical characterization. Commercially available poly(-lactic acid) (Dow-Cargill PLLA, Minneapolis, MN, USA, Mn of 79 kg·mol−1 ) was used without further purification. For PTMC synthesis polymer-grade 1,3-trimethylene carbonate (TMC) (Boehringer Ingelheim, Ingelheim am Rhein, Germany) and stannous octoate (SnOct2 ) (stannous 2-ethylhexanoate) (Sigma, San Jose, CA, USA) were used as received. Poly(trimethylene carbonate) (PTMC) was synthesized in dried, freshly silanized (Serva solution, Boehringer Ingelheim, Ingelheim am Rhein, Germany) glass ampoules. The ampoules were purged with dry argon, charged with monomer and catalyst (2 × 10−4 mol SnOct2 per mol TMC), and heat-sealed under vacuum. The polymerizations were conducted at 130 ± 1 ◦ C for 3 d. The polymers were purified by precipitating their chloroform solutions into methanol and then dried [2]. For synthesis of copolymers lactide and carbonate were used. Lactide monomer of DLA (Boehringer Ingelheim, Ingelheim am Rhein, Germany) was crystallized from dry 2-propanol and then purified by sublimation in vacuum (10−3 mbar, 90 ◦ C). TMC (Boehringer Ingelheim, Ingelheim am Rhein, Germany, >99%) was crystallized from dry tetrahydrofuran/ethyl ether mixture (3/1) and sublimed (10−3 mbar, 45 ◦ C). THF (Sigma-Aldrich, Darmstadt, Germany) solvent was purified as described previously [41]. Aluminum tris-isopropoxide (Al(OiPr)3 ) used in a form of its trimer ({Al[OCH(CH3 )2 ]3 }3 was prepared from the commercial alkoxide (Sigma-Aldrich, Saint Louis, MO, USA, 98%) as described elsewhere [42]. Bidendate ligand, (R)-(−)-2,20 -[1,10 -binaphtyl-2,20 -diylbis(nitrylomethilidyne)] diphenolate (SB(OH)2 ), was prepared as described in ref. [43]. Synthesis of copolymers followed the procedure given below [44]. Reacting mixtures were prepared in sealed glass vessels using a standard high vacuum technique. Breakseals equipped with glass hammers, which separately contained Al(OiPr)3 and monomers, were sealed in the reaction glass vessel. Tetrahydrofuran (THF) was distilled into this vessel under vacuum. The SBO2 Al-OiPr initiator is formed in situ from the equimolar quantities of SB(OH)2 and Al(OiPr)3 , kept for 24 h in THF as solvent at 80 ◦ C

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just before use. The breakseals that contained monomers then were broken and all components were mixed at room temperature. The resulting reaction mixture was distributed into a several glass vials, and placed into a thermostat at 80 ◦ C. The random copolymers of DLA and TMC were obtained via simultaneous ring-opening polymerization (ROP) initiated with Al(OiPr)3 , with segmental exchange side reaction. The diblock copolymers were synthetized via sequential ROP in the presence of (R)-SBO2 Al-OiPr, proceeding with suppression of segmental exchange. The resulting copolymers were precipitated into cold methanol, separated, and dried in vacuum at room temperature to a constant weight. 2.2. Preparation of Samples and Irradiation The copolymers were dissolved in chloroform at 20 wt % and solutions were drop-casted to form films of ca. 50 µm thickness. The films were dried to constant weight at room temperature under vacuum. The film samples were vacuum-sealed in plastic bags making barrier to limit air contact and irradiated by electron beam (6 MeV linear accelerator) at room temperature. The dose rate was 5 kGy·min−1 (as determined by alanine dosimetry) and the applied absorbed doses were up to 300 kGy. Alternatively, for EPR investigations, the copolymers were irradiated with an electron beam (7 MeV linear accelerator) to 30 kGy at the dose rate of 10 kGy·min−1 (determined by alanine dosimetry) in plastic pouches without air access at dry-ice temperature and transferred to EPR quartz capillary immediately after irradiation under neutral gas atmosphere (Ar). 2.3. Analytical Procedures Infrared spectra were obtained on an Nicolet Avatar TM 330 FT-IR Spectrometer (Thermo Electron Corporation, Waltham, MA, USA) in the HATR mode. Approximately 0.4 ml of 0.1% polymer solution in chloroform was casted onto the IR transmitting window (80 mm × 10 mm ZnSe plate) to form a uniform layer. The plates were dried for 24 h to remove traces of solvent before spectra acquisition. Spectra were collected with a resolution of 4 cm−1 and with 64 scans per sample over the range of 4000–500 cm−1 . The polymer samples were analyzed by proton nuclear magnetic resonance (1 H-NMR) spectroscopy using a 500 MHz Bruker spectrometer (Billerica, MA, USA) with dichloromethane-d2 as the solvent. Intrinsic viscosities ([η]) of copolymers were determined in chloroform at 25.0 ◦ C with an AVS-310 automatic viscometry system (Schott Geräte, Mainz, Germany) equipped with a 01/0a type Ubbelohde viscometer (Schott Geräte, Mainz, Germany). Prior to the analysis, the non-irradiated samples were filtered through 0.45 µm pore size filters (Sartorius), while the irradiated samples were analyzed without prior filtration. Gel permeation chromatography (GPC) measurements were conducted using the system equipped with a P580 pump (Dionex, Sunnyvale, CA, USA), two columns of 10 µm and 5 µm pore size (Knauer, Biberach/Baden, Germany) and three detectors: Viscotec Ralls Detector (static light scattering at 90◦ at a wavelength of 670 nm) and Viscotec Dual Detector 250 (refractometer/viscometer, Houston, TX, USA). Dichloromethane was used as the eluent at 30 ◦ C at a flow rate of 0.8 ml·min−1 . Sample concentrations in the range 5–10 g/L and injection volumes of 100 µL were used. All solutions were filtered prior to injection into the GPC through 5 µm PTFE membrane filters (Sartorius). Thermal properties of copolymers were determined by differential scanning calorimetry (Q200 M-DSC, TA Instruments, New Castle, DE, USA). Samples of ca. 5 mg sealed in aluminum pans were analyzed in the temperature range from −60 to 210 ◦ C at a heating rate of 10 ◦ C·min−1 under nitrogen atmosphere. The degree of crystallinity of lactide component (χc ) was calculated using the following formula: ∆H χc = (1) (lactide wt %) ∆Ho

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where ∆H is enthalpy of fusion of examined sample, ∆Ho denotes the enthalpy of fusion of 100% crystalline polylactide sample of 93.6 J·g−1 [45]. Correction on cold crystallization was used whenever necessary. EPR spectra of free radicals in poly(TMC-co-DLA) copolymers were collected at room temperature using an ESP300 spectrometer (Bruker Biospin, Billerica, MA, USA) with the following instrument parameters: microwave frequency of 9.42 GHz, microwave power 0.5 mW, frequency modulation 100 kHz, modulation amplitude 3.12 G, receiver gain 6.32 × 103 , center field at 3350 G, sweep width 500 G, conversion time 40.96 ms, and time constant 20.48 ms. It was verified that the modulation amplitude, as well as the ratio of the conversion time to time constant, did not distort the signal. The relative concentration of radicals was determined by double integration of signals recorded directly upon irradiation and after different time. The spin concentration in irradiated samples was determined following procedures described in [46]. 3. Results and Discussion 3.1. Synthesis of Copolymers A series of diblock and random copolymers of PTMC and PDLA was synthesized according to procedures described above (for details see Socka et al. [44]). The polymerization was monitored with NMR and GPC to evaluate the progress and the outcome of the synthesis. Targeted molecular composition is presented in Table 1 together with actual composition of the obtained copolymers, as determined by NMR, degree of monomer conversion and average molecular weights evaluated by GPC. The molecular composition of the copolymers synthesized with high yield was in good agreement with the targeted one. The microstructure of polymers resulted from simultaneous polymerization of two monomers, in terms of average lengths of DLA and TMC microblocks revealed average, yet satisfactorily randomness [44]. Molecular weights of diblock copolymers were of standard level that can be obtained by sequential polymerization, therefore the anticipated molecular weights of random copolymers were at similar level. Table 1. Characteristics of trimethylene carbonate (TMC) and d-lactide (DLA) copolymers used in the study.

Type of Copolymer Poly(TMC-b-DLA) Poly(TMC-b-DLA) Poly(TMC-b-DLA) Poly(TMC-rand-DLA) Poly(TMC-rand-DLA) a

TMC Fraction [mol %] Feed

Actual

36 59 81 59 81

36 59 81 58 81

Conv. [%] 98 99 99 100 100

LDLA 13.0 3.8

a

LTMC 6.6 14.0

a

Mn

Mw

M w /M n

19 24 18 18 17

31 47 35 20 19

1.63 1.96 1.94 1.11 1.12

Average length of the LA and TMC microblocks calculated with 13 C NMR [44].

3.2. Irradiation Effects on the Structure of Copolymers To confirm the incorporation of the monomers in the synthesized copolymers, a series of FT-IR measurements were conducted. FT-IR spectra of PLA and PTMC homopolymers and their copolymers of various compositions are presented in Figure 1 (black lines). Spectra of PLA are characterized by bands at 1750 and 1180 cm−1 assigned to carbonyl and ether bonds, respectively [47]. Similarly, the carbonyl and ether bonds of PTMC are detected at 1741 and 1242 cm−1 [48]. In the spectra of the poly(TMC-b-DLA) copolymers the vibration of the ether bonds can be seen as two bands at 1184 and 1244 or 1242 cm−1 for copolymers containing 36% and 59% of PTMC, respectively. These bands correspond to those observed in individual homopolymers. For block copolymer of the highest PTMC content the band at 1242 cm−1 dominates and the ether band of PDLA cannot be discerned. Due to the overlapping of the carbonyl bands in both homopolymers, in block copolymers we observe only one signal at 1744–1748 cm−1 . Also, the spectra of random copolymers look similar, with two

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copolymers we observe only one signal at 1744–1748 cm−1. Also, the spectra of random copolymers look similar, with two discernible ether bands for 59% PTMC and only one visible for 81% PTMC, discernible ether bands for 59% PTMC and only one visible for 81% PTMC, and a single carbonyl band and a single carbonyl band at 1742–1750 cm−1. at 1742–1750 cm−1 . Figure 1 shows the FT-IR spectra of the irradiated copolymers and polymers at dose level of 100 Figure 1 shows the FT-IR spectra of the irradiated copolymers and polymers at dose level of kGy. Figure 2, however, shows the FT-IR spectra of the irradiated poly(TMC-rand-DLA) (41/59) 100 kGy. Figure 2, however, shows the FT-IR spectra of the irradiated poly(TMC-rand-DLA) (41/59) copolymer with e-beam, at dose levels of 10, 25, 50, 200, and 300 kGy. Additionally, comparison of copolymer with e-beam, at dose levels of 10, 25, 50, 200, and 300 kGy. Additionally, comparison spectra recorded for the initial sample and samples subjected to EB irradiation up to 300 kGy is of spectra recorded for the initial sample and samples subjected to EB irradiation up to 300 kGy is presented in Figure 2 for an example of the random copolymer containing 59% PTMC. The FT-IR presented in Figure 2 for an example of the random copolymer containing 59% PTMC. The FT-IR spectra of all irradiated and un-irradiated poly(TMC-b-DLA) and poly(TMC-rand-DLA) copolymers, spectra of all irradiated and un-irradiated poly(TMC-b-DLA) and poly(TMC-rand-DLA) copolymers, and PTMC, PDLA polymers exhibit similar absorption bands up to 300 kGy, demonstrating that and PTMC, PDLA polymers exhibit similar absorption bands up to 300 kGy, demonstrating that irradiation does not significantly alter their chemical structures. irradiation does not significantly alter their chemical structures. 1.2

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Figure 1. FT-IR spectra of PDLA (a), PTMC (b), poly(TMC-b-DLA) diblock copolymers of different Figure 1. FT-IR spectra of PDLA (a), PTMC (b), poly(TMC-b-DLA) diblock copolymers of different PTMC content ((c)-36%, (d)-59%, (e)-81%) and poly(TMC-rand-DLA) random copolymers of different PTMC content ((c)-36%, (d)-59%, (e)-81%) and poly(TMC-rand-DLA) random copolymers of different PTMC content ((f)-59%, (g)-81%) before irradiation (black and lower lines) and after irradiation at PTMC content ((f)-59%, (g)-81%) before irradiation (black and lower lines) and after irradiation at 100 kGy (red and upper lines). 100 kGy (red and upper lines).

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Figure 2. FT-IR spectra of poly(TMC-rand-DLA) (59/41) copolymers after irradiation at 0–300 kGy. Figure Figure2.2.FT-IR FT-IRspectra spectraofofpoly(TMC-rand-DLA) poly(TMC-rand-DLA)(59/41) (59/41)copolymers copolymersafter afterirradiation irradiationatat0–300 0–300kGy. kGy.

H NMR spectrum of the exemplary block copolymer poly(TMC-b-DLA) 59/41 is shown in 1 1H NMR NMR spectrum ofthe theexemplary exemplary blockcopolymer copolymer poly(TMC-b-DLA) 59/41 is isshown shown spectrum block poly(TMC-b-DLA) 59/41 Figure H 3. The spectrum is of characterized by typical signals of PDLA main chain methine protons atinin Figure 3. The is characterized by typical signals of PDLA main chain methine protons Figure 3. The spectrum characterized by typical signals of PDLA main chain methine protons 5.12 ppm (–CH–), main chain methyl protons at 1.6 ppm (–CH3), PTMC main chain methylene at main chain protons 1.6 2ppm ppm (–CH PTMC main chain methylene at5.12 5.12ppm ppm(–CH–), (–CH–), main chain methyl methyl protons (–CH PTMC main chain methylene protons adjacent to the carbonate group at δ 4.22 at(–CH –CO–) and33),),PTMC main chain methylene protonsatadjacent adjacent thecarbonate carbonate groupatatδminor δ4.22 4.22(–CH (–CH 2–CO–)and andPTMC PTMC main chain1.29 methylene protons totothe –CO–) chain methylene protons δ = 2.03 (quintet, –CHgroup 2–). The but signalmain at about ppm 2well-defined protons at δ = 2.03 (quintet, –CH 2–). The minor minor but well-defined signal at about 1.29 ppm 1 protons at δ = 2.03 (quintet, –CH –). but well-defined signal at about 1.29 corresponds to the tail-end-initiator residue (-CH(CH3)2). Figure 3 shows the H NMR spectra ppm for 2 1H NMR spectra for 1 corresponds to the tail-end-initiator residue (-CH(CH 3 ) 2 ). Figure 3 shows the corresponds to the tail-end-initiator residue (-CH(CH Figure of 3 shows the H NMR spectra for irradiated poly(TMC-b-DLA) 59/41 with 300 kGy. The NMR all copolymers irradiated and 3 )2 ). spectra irradiated poly(TMC-b-DLA) 59/41 with 300 kGy. The NMR spectra of all copolymers irradiated and 1 irradiated poly(TMC-b-DLA) 59/41 with 300 kGy. The NMR spectra of all copolymers irradiated and un-irradiated exhibit similar bands (data not presented here). Similarly, to the FT-IR results, the H 1H 1 un-irradiated exhibit similar bands (data not presented here). Similarly, to the FT-IR results, the un-irradiated exhibit similar bands (dataare notno presented here). Similarly, the FT-IR results, of thetheH NMR results also demonstrated that there significant changes in the to chemical structures NMRresults results alsodemonstrated demonstrated that there areno nosignificant significant changes thechemical chemicalstructures structures the NMR that there are changes ofofthe irradiated andalso un-irradiated homoand copolymers. Irradiation withinin athe sterilization dose (25 kGy) irradiated and un-irradiated homoand copolymers. Irradiation with a sterilization dose (25 kGy) irradiated and un-irradiated homoand copolymers. Irradiation with a sterilization dose (25 kGy) does not influence the structure of the polymers to an extent which would compromise their doesnot not influence structure the polymers to anwhich extentwould which would compromise their does influence the the structure of theofpolymers to an extent compromise their chemistry. chemistry. chemistry. 1

300kGy 300kGy 0kGy 0kGy 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 5.0 4.5 4.0 [ppm] 3.5 3.0 2.5 2.0 1.5 [ppm] 1H

Figure3.3.1H NMR NMRspectra spectraofofthe thepoly(TMC-b-DLA) poly(TMC-b-DLA)59/41 59/41diblock diblockcopolymer, copolymer,unirradiated unirradiatedand and Figure 1H NMR irradiated with a dose of 300 kGy. Figure 3. spectra of the poly(TMC-b-DLA) 59/41 diblock copolymer, unirradiated and irradiated with a dose of 300 kGy. irradiated with a dose of 300 kGy.

3.3.Intrinsic IntrinsicViscosity Viscosity 3.3. 3.3. Intrinsic Viscosity thiswork work intrinsic viscosity measurements were carried outqualitatively to qualitatively investigate InInthis intrinsic viscosity measurements were carried out to investigate the In this intrinsic viscosity measurements carried outreactions toreactions qualitatively investigate the the presence and absence the absence of the crosslinking and degradation homo-and and presence and work the of the crosslinking andwere degradation in inthethe homopresence and the absence of the crosslinking and degradation reactions in the homoand copolymers as a function of dose. Figure 4 shows PTMC’s [η] increases sharply with increasing copolymers as a function of dose. Figure 4 shows PTMC’s [η] increases sharply with increasing dose. copolymers as a demonstrate function of dose. 4 shows PTMC’s [η]PTMC increases sharplymainly with increasing dose. dose. Thesedemonstrate data incase the case of homopolymers, PTMC undergo mainly crosslinking These data that inthat theFigure of homopolymers, undergo crosslinking These data demonstrate thatradiation in the case of homopolymers, PTMC undergo mainly crosslinking reactions. Onthe theother otherhand, hand, radiation induces degradation PDLA. thecase case copolymers, reactions. On induces degradation inin PDLA. InInthe ofofcopolymers, reactions. On the other hand, radiation induces degradation in PDLA. In the case of copolymers, however, crosslinking and scissions take place as a function of their compositions. Figure 4 also however, crosslinking and scissions take place as a function of their compositions. Figure 4 also

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however, crosslinking and scissions take place as a function of their compositions. Figure 4 also shows shows that the copolymers contain 36% 59% and 59% poly(TMC-b-DLA) undergo degradation. that the copolymers whichwhich contain 36% and poly(TMC-b-DLA) undergo degradation. OnOn the the contrary, 81% poly(TMC-rand-DLA) undergoes crosslinking as evidenced by the increase in the contrary, 81% poly(TMC-rand-DLA) undergoes crosslinking as evidenced by the increase in the [η] [η] Slight increase in [η] be detected in the 81% poly(TMC-b-DLA). Slight increase in [η] cancan alsoalso be detected in the 81% poly(TMC-b-DLA). PLA PTMC 35/65 Poly(TMC-b-DLA) 59/41 Poly(TMC-b-DLA) 59/41 Poly(TMC-rand-DLA) 81/19 Poly(TMC-b-DLA) 81/19 Poly(TMC-rand-DLA)

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300

Dose [kGy]

Figure 4. 4. Relative Relative change change of of the — intrinsicviscosities, viscosities,after afterirradiation irradiationto to Figure the intrinsic intrinsic viscosity viscosity (η/η (η/η00—intrinsic initial) of diblock and random copolymers compared to those of homopolymers as a function of initial) of diblock and random copolymers compared to those of homopolymers as a function of absorbeddose. dose. absorbed

3.4.Molecular MolecularWeight Weight 3.4. Theinitial initialmolecular molecularweights weightsofof the synthesized copolymers were relatively low, in the order The the synthesized copolymers were relatively low, in the order of a few kDa, compared thehomopolymers. homopolymers.It Itshould shouldbebementioned, mentioned,that thatthe themain main aoffew tenstens of of kDa, as as compared totothe radiation-inducedeffects effectsininpolymers polymersirradiated irradiatedininsolid solidstate stateare arenot notdependent dependenton onthe themolecular molecular radiation-induced weight, except except for short significant part of the main chain [34]. weight, short oligomers oligomerswhere whereend-groups end-groupscomprise comprise significant part of the main chain Tables 2–4 2–4 show numberand weight-average molecular and irradiated irradiated [34]. Tables show numberand weight-average molecularweights weightsof of unirradiated unirradiated and homopolymersand andcopolymers. copolymers. homopolymers As demonstrated by viscosity measurements, radiation-induced degradationdegradation is predominant As demonstratedearlier earlier by viscosity measurements, radiation-induced is for PDLA, while reaction mainlyreaction takes place in PTMC. of high PDLA content predominant for crosslinking PDLA, while crosslinking mainly takesCopolymers place in PTMC. Copolymers of poly(TMC-b-DLA) poly(TMC-b-DLA) (59/41) and poly(TMC-rand-DLA) (59/41)) undergo high PDLA content (35/65), poly(TMC-b-DLA) (35/65), poly(TMC-b-DLA) (59/41) and poly(TMC-rand-DLA) degradation. Thesedegradation. results show that molecular weight dispersion (Mw /Mn )weight increasesdispersion in all cases. (M While (59/41)) undergo These results show that molecular w/Mfor n) the random it doesfor notthe exceed 2, it becomes higher thannot 2 for the block Should only increases in copolymer all cases. While random copolymer it does exceed 2, it copolymers. becomes higher than 2 random scissions take place in these samples, one would expect that (M /M ) would approach value for the block copolymers. Should only random scissions take place in w these n samples, one would of 2 [49], but ton)exceed value. value The observed increase of to Mw /Mn higher than 2The indicates that expect that (Mnot w/M wouldthis approach of 2 [49], but not exceed this value. observed scissions are by less crosslinking reactions, which leads to significant broadening of increase of accompanied Mw/Mn higher thanprobable 2 indicates that scissions are accompanied by less probable molecular weight distribution. Sinceto Msignificant not exceed 2ofinmolecular the dose range of 10–300 kGy, itSince is still crosslinking reactions, which leads weight distribution. w /Mn doesbroadening not clear, if poly(TMC-rand-DLA) (59/41) scission and crosslinking simultaneously. M w/M n does not exceed 2 in the dose range of 10–300 kGy, it is stilloccur not clear, if poly(TMC-rand-DLA) An increase in the average molecular weight is observed for both copolymers of the highest PTMC (59/41) scission and crosslinking occur simultaneously. content poly(TMC-b-DLA) (81/19) and poly(TMC-rand-DLA) to the viscosity results, An — increase in the average molecular weight is observed(81/19). for bothSimilar copolymers of the highest a relative increase in molecular weights is higher the random copolymer.(81/19). Similar to the PTMC content—poly(TMC-b-DLA) (81/19) andforpoly(TMC-rand-DLA) Attention be paid to theineffects of irradiation the dose of 25 kGy which is regarded as viscosity results,should a relative increase molecular weights with is higher for the random copolymer. typical sterilization dose. While is effects evidentofthat application radiation sterilization of Attention should be paid to it the irradiation withofthe dose ofas 25akGy which is method regarded biomaterials and medical polylactidesoforradiation copolymers majority as typical sterilization dose.devices While comprising it is evident pure that application as a containing sterilizationa method of biomaterials polylactides is rather unfeasible, demonstrated poly(TMC-co-DLA)copolymers of high of and medical devicesit is comprising purethat polylactides or copolymers containing a PTMC content do not degrade even can it beiscrosslinked by electron beam when irradiated with majority of polylactides is ratheror unfeasible, demonstrated that poly(TMC-co-DLA)copolymers 25high kGyPTMC and higher doses. In degrade irradiated crosslinking chain scission of content do not or copolymers even can be intermolecular crosslinked by electron beamand when irradiated occur25simultaneously, however of PTMC segments or monomer units dominates at with kGy and higher doses.the In crosslinking irradiated copolymers intermolecular crosslinking and chain high PTMC content. The observed effect of in molecular weight for PTMC-rich copolymer scission occur simultaneously, however theincrease crosslinking of PTMC segments or monomer units resembles,atbut it PTMC is not content. that pronounced, thateffect occurring in PTMC homopolymer. In PTMC-rich the case of dominates high The observed of increase in molecular weight for copolymer resembles, but it is not that pronounced, that occurring in PTMC homopolymer. In the case of neat PTMC an increase in molecular weight eventually leads to formation of insoluble fraction. Macromolecules become chemically crosslinked to form stable gel, which in turn enhances

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neat PTMC an increase in molecular weight eventually leads to formation of insoluble fraction. Macromolecules become chemically crosslinked to form stable gel, which in turn enhances mechanical properties of materials based on PTMC [37]. It is anticipated that lactide biomaterials can withstand radiation sterilization when combined with crosslinking-type co-component. As compared to blending of two polymers, copolymerization seems to be better solution to obtain mixture at molecular level. Table 2. Number-average and weight-average molecular weights [kg·mol−1 ] and molecular weight dispersion of PTMC and PDLA homopolymers as a function of dose.

Dose [kGy] 0 10 25 50 100 200

PTMC

PLA

Mn

Mw

M w /M n

Mn

Mw

M w /M n

108.9 124.4 136.5 142.6 162.3 202.5

270 260 277 290 308 336

2.48 2.09 2.03 2.03 1.90 1.66

215 90 62 45 30

260 105 96 70 68

1.21 1.17 1.55 1.56 2.27

Table 3. Number-average and weight-average molecular weights [kg·mol−1 ] and molecular weight dispersion of poly(TMC-b-DLA) diblock copolymers of various composition (in mol %). Poly(TMC-b-DLA) 81/19

Dose [kGy] 0 10 25 50 100 200 300

Mn

Mw

19 30 28 29 50 65

31 56 43 41 78 82

59/41 M w /M n M n 1.63 1.87 1.54 1.41 1.56 1.26

Mw

24 23 21 18 16 13 10

47 45 44 37 39 29 23

36/64 M w /M n M n 1.96 1.96 2.10 2.06 2.44 2.23 2.30

18 17 15 14 12 9 7

Mw

M w /M n

35 32 31 30 27 19 19

1.94 1.88 2.07 2.14 2.25 2.11 2.71

Table 4. Number-average and weight-average molecular weights [kg·mol−1 ] and molecular weight dispersion of poly(TMC-rand-DLA) random copolymers, of various composition (in mol %). Poly(TMC-rand-DLA) 81/19

Dose [kGy] 0 10 25 50 100 200 300

59/41

Mn

Mw

M w /M n

Mn

Mw

M w /M n

18 19 28 31 39 43

20 21 30 35 46 49

1.11 1.11 1.07 1.13 1.18 1.14

17 14 12 12 10 7 6

19 16 15 15 13 10 9

1.12 1.14 1.25 1.25 1.30 1.43 1.50

To characterize crosslinking and scission processes occurring in the irradiated polymers, the respective radiation-chemical yields were determined. These important parameters of radiation sensitivity of a particular polymer, radiation chemical yields of chain scission Gs and intermolecular cross-linking Gx , are defined as the number of moles of scission events or formed crosslinks per

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unit of absorbed energy. In the polymeric systems where chain scission and crosslinking take place simultaneously, radiation yields can be calculated from the following equations [50]

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1 1 Gs = + ( − 2Gx )· D (2) Mw1 M1w0 2 = + (𝐺s − 𝐺x ) ∙ 𝐷 (3) 𝑀n 𝑀n0 1 1 = + ( Gs − Gx )· D (3) where: Mw0 and Mn0 are the initial weightMn and Mn0number-average molecular weights of the polymer, M w and Mn are the weight- and number-average molecular weights of irradiated samples (all in where: Mw0 and Mn0 are the initial weight- and number-average molecular weights of the polymer, Mw kg/mol), D isthe theweightabsorbed Gx is the yield of crosslinking, the yieldsamples of chain(all scission (both and Mn are anddose, number-average molecular weightsGofs is irradiated in kg/mol), −1). While Equation (3) can be used for any molecular-weight distribution of the initial in mol· J D is the absorbed dose, Gx is the yield of crosslinking, Gs is the yield of chain scission (both in mol·J−1 ). samples, Equation (2)be is used strictly truemolecular-weight only if Mw0/Mn0distribution = 2. Since of this is notEquation fulfilled(2) for While Equation (3) can for any thecondition initial samples, is majority of our samples, we limit the analysis to calculating the value of G x-Gs, which can be taken as strictly true only if Mw0 /Mn0 = 2. Since this condition is not fulfilled for majority of our samples, we limit an inthe thevalue polymeric subjected to irradiation crosslinking predominates theindication analysis to whether calculating of Gx -Gsystem s , which can be taken as an indication whether in the polymeric over scission. The results for homopolymers and poly(TMC-co-DLA) arehomopolymers illustrated in system subjected to irradiation crosslinking predominates over scission. copolymers The results for Figure 5. The dominance of crosslinking over in chain scission of and poly(TMC-co-DLA) copolymers are illustrated Figure 5. The reactions dominanceinofirradiated crosslinkingsamples over chain copolymers containing higher content of the carbonate blocks is ascertained. The average G x-Gs scission reactions in irradiated samples of copolymers containing higher content of the carbonate blocks is values, the difference ofGradiation yields of cross-linking and scission, for PTMC-rich (81 mol %) ascertained. The average x -Gs values, the difference of radiation yields of cross-linking and scission, for 7 mol·J−1 and 0.22 × 10−7 mol·J−1, respectively, for diblock copolymers were calculated to be 0.27 × 10 PTMC-rich (81 mol %) copolymers were calculated to be 0.27 × 107 mol·J−1 and 0.22 × 10−7 mol·J−1 , and random copolymers, whereas for the PTMC homopolymer was over × respectively, for diblock and random copolymers, whereas for the the yields PTMCdifference homopolymer the 0.35 yields −7 −1 10 mol·J was within dose range. The average Gx-G s values for copolymers with difference overinvestigated 0.35 × 10−7absorbed mol·J−1 within investigated absorbed dose range. The average Gx -Gs −7 mol·J−1 and lower content of PTMC, 59 mol %, are negative, and were determined to beand −0.21 × 10determined values for copolymers with lower content of PTMC, 59 mol %, are negative, were to −7 −0.26 × 10 J−1 ·for and random respectively. they are still −7 mol −7 mol·copolymers, be −0.21 × 10mol· J−1 diblock and −0.26 × 10 J−1 for diblock and randomNaturally, copolymers, respectively. −7 mol·J−1, since crosslinking is minor for somewhat higher obtained for neat −0.32 × 10for Naturally, they arethan still that somewhat higher thanPLA, that obtained neat PLA, −0.32 × 10−7 mol·J−1 , since poly(lactic acid). crosslinking is minor for poly(lactic acid). PTMC

(Gx-Gs) [10-7mol/J])

0.2

Random 0.0

TMC / DLA 59 / 41

Degradation

Diblock

TMC / DLA 81 / 19

Crosslinking

0.4

Diblock

-0.2

Random -0.4

PLA 0

50

100

150

200

250

300

Dose [kGy]

Figure 5. 5. Difference Difference radiation x -G s ) for homo- and co-polymers of Figure radiation yields yieldsof ofcrosslinking crosslinkingand andscission scission(G(G x-Gs) for homo- and co-polymers PTMC and PDLA as a function of dose. of PTMC and PDLA as a function of dose.

3.5. Thermal Thermal Properties Properties 3.5. DSC heating neat PDLA andand PTMC and their with different content DSC heating thermograms thermogramsofof neat PDLA PTMC and copolymers their copolymers with different of monomers are shown Figurein 6, the first6,heating, Figureand 7 theFigure second7 heating, respectively. content of monomers areinshown Figure the firstand heating, the second heating, Two heat effects at temperatures corresponding to the glass transition temperature (T ) and melting g respectively. Two heat effects at temperatures corresponding to the glass transition temperature (Tg) temperature and block copolymers. homopolymer and random m ) can be observed and melting(Ttemperature (Tm) the canPDLA be observed the PDLA PTMC and block copolymers. PTMC copolymer of 81/19 amorphous, whereas of 59/41 molar composition displays some crystalline homopolymer and are random copolymer of that 81/19 are amorphous, whereas that of 59/41 molar phase. Depending on the composition, the glass transition temperatures of the copolymers vary composition displays some crystalline phase. Depending on the composition, the glass transition ◦ ◦ between the Tof PTMC (approximately −21 the C) [41] the T(approximately g of g of PDLA (approximately temperatures the copolymers vary between Tg ofand PTMC −21 °C) [41] 61 andC) the[51]. Tg Glass transition of both blocks is observed in the first heating thermograms at temperatures of ca. of PDLA (approximately 61 °C) [51]. Glass transition of both blocks is observed in the first heating ◦ C for PTMC segments and at temperatures of 45–50 ◦ C for PDLA segments, (Figure 6 − 19 ÷ − 13 thermograms at temperatures of ca. −19 ÷ −13 °C for PTMC segments and at temperatures of 45–50 black The Tg of both segments slightly increased an increase lactide content. In with random °C forline). PDLA segments, (Figure 6 black line). The Tg with of both segmentsinslightly increased an increase in lactide content. In random copolymer of the molar percentage ratio poly(TMC-rand-DLA) 59/41 two glass transitions at −6.3 and 44.5 °C were also detected, but for poly(TMC-rand-DLA) (81/19) only a single glass transition was observed at −8.8 °C. Lower randomness of 59/41 copolymer (0.19; in the scale where 0 is block and 1 is fully random copolymer) resulted in occurrence of two glass transitions representing separated phases of PTMC and PDLA segments [44]. The randomness

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copolymer of the molar percentage ratio poly(TMC-rand-DLA) 59/41 two glass transitions at −6.3 and 44.5 ◦ C were also detected, but for poly(TMC-rand-DLA) (81/19) only a single glass transition was ◦ C. Lower randomness of 59/41 copolymer (0.19; in the scale where 0 is block and observed at − Polymers 2018, 10,8.8 x FOR PEER REVIEW 11 of 21 Polymers 2018, 10, x FOR PEER REVIEW 11 of 21 1 is fully random copolymer) resulted in occurrence of two glass transitions representing separated of the of copolymer chain has a value[44]. of 0 in randomness the case of block copolymer chain and 1 in athe case 0ofina phases PTMC and PDLA of the copolymer copolymer value of the copolymer chain hassegments a value of 0The in the case of block and 1has in the caseofof a completely random distribution the copolymer repeating units. the case of block copolymer and of 1ofin case of a completely random distribution of the copolymer completely random distribution thethe copolymer repeating units. Concerning the second heating the only one Tg transition for all the copolymers (Figure 7) was repeating units. the Concerning second heating the only one Tg transition for all the copolymers (Figure 7) was detected. It relates tosecond stresses generated due to difference in thermal expansion of both constituents. Concerning the the due only one Tg transition for allexpansion the copolymers 7) was detected. It relates to stressesheating generated to difference in thermal of both(Figure constituents. The first heating thermograms for the diblock and randomincopolymers shows only one constituents. endothermal detected. It relates to stresses generated due to difference thermal expansion of both The first heating thermograms for the diblock and random copolymers shows only one endothermal transition of melting (at Tm), whereas second and heating of the diblock copolymer thermogram shows, The first heating thermograms for the diblock random shows only one endothermal transition of melting (at Tm), whereas second heating of thecopolymers diblock copolymer thermogram shows, along with melting, additional cold crystallization (at T c ). Cold crystallization is an exothermic transition melting (at Tm ), whereas second heating(at of the copolymer thermogram shows, along withofmelting, additional cold crystallization Tc).diblock Cold crystallization is an exothermic crystallization process. It is observed on heating a (at sample that has previously been cooled very along with melting, additional cold crystallization T ). Cold crystallization is an exothermic c crystallization process. It is observed on heating a sample that has previously been cooled very quickly and has had noIt time to crystallize. Below the glass transition, molecular mobility is severely crystallization process. is observed on heating a sample that has previously been cooled very quickly quickly and has had no time to crystallize. Below the glass transition, molecular mobility is severely restricted and cold crystallization does the not glass occur; above the glass transition, small crystallites are and has had nocold timecrystallization to crystallize. Below mobilitysmall is severely restricted restricted and does not occur;transition, above themolecular glass transition, crystallites are formed atcrystallization relatively lowdoes temperatures. Depending of thetransition, composition of copolymers aare heat transfer and cold not occur; above the glass small crystallites formed at formed at relatively low temperatures. Depending of the composition of copolymers a heat transfer resulting from melting of the PDLA indicates its crystalline phase. Detailed comparison of thermal relatively low temperatures. of theits composition of copolymers heat transferofresulting resulting from melting of theDepending PDLA indicates crystalline phase. Detailedacomparison thermal parameters for copolymers of PTMC and PDLA was presented incomparison our previous work [44]. from melting of the PDLA indicates its crystalline phase. Detailed thermal parameters for copolymers of PTMC and PDLA was presented in our previousofwork [44].parameters Thermograms of the irradiated diblock copolymers (red lineswork in Figures and 7 for first and for copolymers of PTMC PDLA was presented in our (red previous [44]. 66 and Thermograms of theand irradiated diblock copolymers lines in Figures 7 for first and second heating, respectively) show some difference in shapes of the peaks related to7 their melting Thermograms of the irradiated diblock copolymers (red lines in Figures 6 and for first and second heating, respectively) show some difference in shapes of the peaks related to their melting temperatures. However, there is some no alternation ofshapes the shapes of the random copolymers second heating, respectively) show difference in of the peaks related to their melting temperatures. However, there is no alternation of the shapes of the random copolymers thermograms. temperatures. thermograms. However, there is no alternation of the shapes of the random copolymers thermograms. 81/19 81/19

Tm PDLA Tm PDLA

0kGy 0kGy

100kGy 100kGy

Exo Exo

0 0

(a) (a)

25 50 75 100 125 150 175 200 25 50 75 100 125 150 175 200 Temperature [C] Temperature [C]

0kGy 0kGy

81/19 81/19

59/41 59/41

36/64 36/64

Exo Exo

-50 -25 -50 -25

Tg PDLA Tg PDLA

Heat flow Heat flow

Heat flow Heat flow

Heat flow Heat flow

PDLA PDLA

Tg PTMC Tg PTMC

Poly(TMC-b-DLA) Poly(TMC-b-DLA) -50 -25 0 25 50 75 100 125 150 175 200 -50 -25 0 25 50Temperature 75 100 [C] 125 150 175 200 Temperature [C]

(b) (b)

(c) (c)

Tg PTMC Tg PTMC 59/41 59/41

100kGy 100kGy Tg PDLA Tg PDLA

Tm PDLA Tm PDLA

Exo Exo

PTMC PTMC

Poly(TMC-rand-DLA) Poly(TMC-rand-DLA) -50 -25 0 25 50 75 100 125 150 175 200 -50 -25 0 25 50 75 100 Temperature [C] 125 150 175 200 Temperature [C]

Figure 6. DSC first heating thermograms of homopolymers (a), diblock copolymers (b) and random Figure 6. DSC first heating thermograms of homopolymers (a), diblock copolymers (b) and random copolymers (c) with different content of comonomers TMC/DLA. copolymers (c) with different content of of comonomers comonomers TMC/DLA. TMC/DLA.

59/41 59/41 Heat flow Heat flow

Heat flow Heat flow

PDLA PDLA

36/64 36/64

Tg PTMC Tg PTMC

Tmz PDLA Tmz PDLA Tm PDLA Tm PDLA

0kGy 0kGy

81/19 81/19

Heat flow Heat flow

81/19 81/19

PTMC PTMC

0kGy 0kGy

100kGy 100kGy

59/41 59/41

Tg Tg

(a) (a)

0 0

25 50 75 100 125 150 175 200 25 50 75 100 Temperature [C] 125 150 175 200 Temperature [C]

(b) (b)

Poly(TMC-b-DLA) Poly(TMC-b-DLA) -50 -25 0 25 50 75 100 125 150 175 200 -50 -25 0 25 50 75 100 Temperature [C] 125 150 175 200 Temperature [C]

(c) (c)

Exo Exo

-50 -25 -50 -25

Exo Exo

Exo Exo

100kGy 100kGy Poly(TMC-rand-DLA) Poly(TMC-rand-DLA) -50 -25 0 25 50 75 100 125 150 175 200 -50 -25 0 25 Temperature 50 75 100 [C] 125 150 175 200

Temperature [C]

Figure 7. DSC second heating thermograms of homopolymers (a), diblock copolymers (b) and Figure 7. DSC second heating thermograms of homopolymers (a), diblock copolymers (b) and Figure 7. copolymers DSC second(c) heating thermograms of homopolymers diblock copolymers (b) and random random with different content of comonomers(a), TMC/DLA. random copolymers (c) with different content of comonomers TMC/DLA. copolymers (c) with different content of comonomers TMC/DLA.

The data in Figure 8 show the glass transition temperature (Tg) of diblock and random The data in Figure 8 show the glass transition temperature (Tg) of diblock and random copolymers of various compositions irradiated to doses of up to 300 kGy. A general observation is The dataof invarious Figure 8compositions show the glass transitionto temperature of diblock random copolymers g ) 300 copolymers irradiated doses of up(Tto kGy. Aand general observation is that after irradiation all glass transitions exist at very similar level as for non-irradiated samples. T g of various compositions irradiated to doses to similar 300 kGy. A as general observation is that after that after irradiation all glass transitions existof at up very level for non-irradiated samples. Tg of TMC component in either block and random copolymers does not change after irradiation. Even if of TMC component in either block and random copolymers does not change after irradiation. Even if the transition point of the non-irradiated random copolymers is shifted towards higher the transition point of the non-irradiated random copolymers is shifted towards higher temperatures due to presence of the co-component segments, it remains at the same level. The temperatures due to presence of the co-component segments, it remains at the same level. The observation is consistent with the literature data for neat PTMC for which Tg is constant through observation is consistent with the literature data for neat PTMC for which Tg is constant through wide range of absorbed doses [37]. Degradation of lactide blocks or segments however, does not wide range of absorbed doses [37]. Degradation of lactide blocks or segments however, does not

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irradiation all glass transitions exist at very similar level as for non-irradiated samples. Tg of TMC component in either block and random copolymers does not change after irradiation. Even if the transition point of the non-irradiated random copolymers is shifted towards higher temperatures due to presence of the co-component segments, it remains at the same level. The observation is consistent with the literature data for neat PTMC for which Tg is constant through wide range of Polymers 2018, 10,[37]. x FORDegradation PEER REVIEW of lactide blocks or segments however, does not result in reduction 12 of 21 absorbed doses of glass transition temperature of the PDLA component, as could be expected. It was reported that was reported that extensive degradation is reflected the decrease in the Tg [40]. This extensive degradation of the PLA is reflectedofinthe thePLA decrease in the Tin g [40]. This may happen if ability may happen if ability of segmental motion is altered due to extensive chains of segmental motion is altered due to extensive degradation — short chains degradation—short formation and creation of formation in and creation of thus end-groups in large number, thus disruption of in polymer chemistry. end-groups large number, disruption of polymer chemistry. Apparently, the present case Apparently, in of thealready presentrelatively case the short degradation already relatively short chains does not the degradation lactide of chains does not change thelactide lability of segments. change the lability of segments. is partially to presence of the carbonate component This is partially related to presenceThis of the carbonaterelated component that absorbs a part of energy whichthat is absorbs a part of weight energy fraction. which is proportional to its weight fraction. proportional to its TMC [% mol] 81 59

TMC [% mol] 81 59

36

60

60

50 40

40

30

30 First heating

20 First heating 10

Glass transition temperature [C]

Glass transition temperature [C]

50

-10 -20 60 50 40 30 20

Second heating

0 -10 -20 60 50

Second heating

40 30 20 10 0

-10

-10 -20

-20 0

(a)

50

100

150

200

Dose [kGy]

250

0

300

(b)

50

100

150

200

250

300

Dose [kGy]

Figure 8. Glass transition temperature of PDLA and PTMC as a function of radiation dose; (a) Figure 8. Glass transition temperature of PDLA and PTMC as a function of radiation dose; (a) diblock diblock and (b) random copolymers. and (b) random copolymers.

PDLA is an intrinsically semicrystalline polymer which exhibits a melting peak at 170–195 °C ◦ is an intrinsically semicrystalline which exhibits melting peak at 170–195 [52]PDLA depending on its isomeric purity, thuspolymer it was expected that itsa block copolymers would Cbe[52] also depending on its isomeric purity, thus it was expected that its block copolymers would be also semicrystalline. A continuous decrease in melting temperature of PLA segments with respect to semicrystalline. A continuous decrease in melting temperature PLA is segments withvisible respect increasing radiation dose is due to polylactide degradation. Theofeffect strong and in to the increasing radiation dose is due to polylactide degradation. The effect is strong and visible in the first and second heating scans (Figure 9). It is preceded by the cold crystallization in the latter case first and second heating (Figure 9). It at is lower preceded by the cold crystallization in the latter case (longer chains of lactidescans blocks crystallize temperature—lower temperature (lesser energy) (longer chains to of lactide blocksthe crystallize lower temperature — lower temperature (lesser energy) is is required re-orientate shorteratchains). Shorter chains possess better movement ability, required to re-orientate the shorter chains). Shorter chains possess better movement ability, therefore therefore partially degraded PLA can adjust into ordered configuration earlier, that is at lower partially degraded PLA can adjust ordered earlier,inthat lower temperature while temperature while heating over into the T g. Evenconfiguration over 5 °C decrease theisTat m was recorded for samples ◦ heating overwith the Tag . relatively Even overhigh 5 C dose decrease in the TmHowever, was recorded forca. samples irradiated a irradiated of 300 kGy. up to 50 kGy the Tm with remains relatively high dose of 300 kGy. However, up to ca. 50 kGy the T remains unchanged, showing that m unchanged, showing that a specific quantity of chains which are degraded is required to result in aTm specific quantity of chains which degraded is required to result in Tm decrease. Oneplays may its expect decrease. One may expect that are plastification effect of newly created shorter chains role,that even plastification effect of newly created shorter chains plays its role, even though it is not demonstrated in though it is not demonstrated in the alternation of the Tg. Random copolymer of the higher lactide content (59/41 TMC/DLA) also exhibited presence of regular segmental arrangement, with relatively low Tm of ca. 126 °C which was further decreasing of about 4 degrees after irradiation with the highest applied dose.

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the alternation of the Tg . Random copolymer of the higher lactide content (59/41 TMC/DLA) also exhibited presence of regular segmental arrangement, with relatively low Tm of ca. 126 ◦ C which was Polymers 2018, 10, x FOR REVIEW 13 of 21 further decreasing ofPEER about 4 degrees after irradiation with the highest applied dose. Poly(TMC-b-DLA) TMC [% mol]) 81

170

59

36

First heating

165 160 155 150

140 160

135

Poly(TMC-rand-DLA) TMC [% mol] 155

130 170 Second heating

Melting temperature [C]

Melting temperature [C]

145

165 160 155 150 145 140

(a)

150 145 140 135 130 125

135 130

First heating

59

120

0

50

100

150

200

Dose [kGy]

250

0

300

50

100

150

200

250

300

Dose [kGy]

(b)

Figure 9. Melting temperature of diblock (a) and random (b) copolymers as a function of absorbed Figure 9. Melting temperature of diblock (a) and random (b) copolymers as a function of absorbed dose. dose.

The The crystallization crystallization ability ability of of these these DLA-based DLA-based copolymers copolymers is is affected affected by by DLA DLA content content and and its its average sequence length; however, this does not change with dose as identified in the first heating. average sequence length; however, this does not change with dose as identified in the first heating. Figure Figure 10 10 shows shows heat heat of of fusion fusion related related to to melting melting of of crystalline crystalline phase phase of of the the lactide, lactide, which which in in the the case case of block copolymers is preceded by cold crystallization. Exothermic peak of cold crystallization of block copolymers is preceded by cold crystallization. Exothermic peak of cold crystallization was was not TMC/DLA.Surprisingly, Surprisingly, the the degree degree of of crystallinity, crystallinity, as not observed observed for for random random copolymers copolymers of of 59/41 59/41 TMC/DLA. as represented only by by the the DLA DLAfraction, fraction,does doesnot notchange changesignificantly significantlywith witheven even high absorbed dose. represented only high absorbed dose. It It is known that poly(lactic acid) slightly increases its degree of crystallinity upon irradiation [30]. is known that poly(lactic acid) slightly increases its degree of crystallinity upon irradiation [30]. Degradation crystallization to larger extent because of easier organization of shorter Degradation usually usuallyfacilitates facilitates crystallization to larger extent because of easier organization of chains. the copolymer with flexible segments as provided by TMC, of DLAofpart is shorter In chains. In the copolymer with flexible segments as provided bycrystallization TMC, crystallization DLA intrinsically high — of ca. 50–65%, thus appearance of shorter chains does not further increase the χ c. part is intrinsically high—of ca. 50–65%, thus appearance of shorter chains does not further increase diblock copolymers with 81% TMC a slight increase in the degree of crystallinity was detected the χFor c. during first heatingcopolymers (Figure 11).with The initial increase in degree of crystallinity is due of to the re-orientation For diblock 81% TMC a slight increase in the degree crystallinity was of the shorter chains of PDLA. In the case of a diblock copolymer with 59% PTMC it was detected during first heating (Figure 11). The initial increase in degree of crystallinity is found due tothat the the degree of crystallinity does not change at initial radiation thencopolymer over 50 kGy a slight re-orientation of the shorter chains of PDLA. In the case of doses, a diblock with 59% decrease PTMC it was was observed. found that the degree of crystallinity does not change at initial radiation doses, then over 50 kGy Thedecrease DSC measurements demonstrated that, even while degradation and crosslinking occur in a slight was observed. the copolymers, the overall thermal properties are controlled rather by the molar composition and The DSC measurements demonstrated that, even while degradation and crosslinking occur in microstructure of copolymers but not by the irradiation. the copolymers, the overall thermal properties are controlled rather by the molar composition and microstructure of copolymers but not by the irradiation.

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Figure 10. Heat of melting (a) and cold crystallization (b) of diblock as a function of absorbed dose. Figure 10. Heat of melting (a) and cold crystallization (b) of diblock as a function of absorbed dose. Figure 10. Heat Heat of of melting melting (a) and cold crystallization (b) of diblock as a function of absorbed dose. 80 80 80 [%] crystallinity ofof Degree crystallinity Degree [%] [%] of crystallinity Degree

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Figure 11. Degree of crystallinity of diblock (a) and random (b) copolymers as a function of absorbed Figure11. 11.Degree Degree of crystallinity of diblock and random (b) copolymers as aoffunction Figure of crystallinity of diblock (a) and(a) random (b) copolymers as a function absorbedof Figure 11. Degree of crystallinity of diblock (a) and random (b) copolymers as a function of absorbed dose. absorbed dose. dose. dose.

3.6. Radiolytically Produced Free Radicals 3.6. 3.6.Radiolytically RadiolyticallyProduced ProducedFree FreeRadicals Radicals 3.6. Radiolytically Produced Free Radicals Based on the chemical structure of the poly(TMC-b-DLA), it is expected that ionizing radiation Based on the chemical structure poly(TMC-b-DLA), ititisisexpected that ionizing radiation Based on on the the chemical chemical structure structureofof ofthe the poly(TMC-b-DLA), that Based thealkoxyl poly(TMC-b-DLA), it is expected expected that ionizing ionizing radiation radiation induces ester bonds scission giving rise to and acetyl radicals, and simultaneously the alkyl induces ester bonds scission giving rise totoalkoxyl and acetyl radicals, and simultaneously the induces ester bonds scission giving rise alkoxyl and acetyl radicals, and simultaneously thealkyl alkyl induces ester bonds scission giving rise to alkoxyl and acetyl radicals, and simultaneously the alkyl radicals are formed in the PTMC segments, as shown below (Figure 12). radicals are formed in the PTMC segments, as shown below (Figure 12). radicals are formed in the PTMC segments, as shown below (Figure 12). radicals are formed in the PTMC segments, as shown below (Figure 12).

Figure 12. Formation of alkoxy and carbon center radicals upon irradiation of poly(TMC-b-DLA). Figure 12. Formation of alkoxy and carbon center radicals upon irradiation of poly(TMC-b-DLA). Figure Figure 12. 12. Formation Formation of of alkoxy alkoxy and and carbon carbon center center radicals radicals upon upon irradiation irradiation of of poly(TMC-b-DLA). poly(TMC-b-DLA).

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AsAs demonstrated inin Figure 12,12, while the probability ofof the ester bonds scission is is proportional demonstrated Figure while the probability the ester bonds scission proportional toto the DLA component with the production ofof alkoxyl and alkyl radicals, the cleavage ofof C–H bonds the DLA component with the production alkoxyl and alkyl radicals, the cleavage C–H bonds along the backbone of the chains becomes more prevailing as the TMC component increases. along the backbone of the chains becomes more prevailing as the TMC component increases. The EPR spectra ofof the irradiated diblock and random copolymers areare presented inin Figure 1313 The EPR spectra the irradiated diblock and random copolymers presented Figure together togetherwith withthe thespectrum spectrumobtained obtainedfor forPLA PLAhomopolymer. homopolymer.InInevery everycase, case,these thesesamples sampleswere were irradiated with electron beam atat total dose ofof 3030 kGy, inin the absence ofof oxygen and inin the presence ofof irradiated with electron beam total dose kGy, the absence oxygen and the presence ◦ C). dry iceice (−78.5 °C). PTMC homopolymer displayed nono measurable spectra, since at at room temperature dry (−78.5 PTMC homopolymer displayed measurable spectra, since room temperature radical irradiationdecayed decayed immediately in amorphous this amorphous polymer. The time radicalcreated created upon irradiation immediately in this polymer. The time evolution evolution of theofspectra of the irradiated diblock copolymers poly(TMC-b-DLA) with TMC/DLA of the spectra the irradiated diblock copolymers poly(TMC-b-DLA) with TMC/DLA 36/64 and 36/64 and TMC/DLA areinshown 14 respectively. Theofchanges of the spectra werein TMC/DLA 81/19 are81/19 shown Figurein 14Figure respectively. The changes the spectra were monitored monitored in the absence of oxygen and at room temperature. It is clear that the EPR spectra the absence of oxygen and at room temperature. It is clear that the EPR spectra of TMC/DLA 36/64 of and TMC/DLA 36/64 andwhich TMC/DLA 81/19, which were measured immediately after irradiation, are TMC/DLA 81/19, were measured immediately after irradiation, are different. For TMC/DLA different. For TMC/DLA 36/64,of where the formation of thehigh alkoxyl relatively high as a result of ether the 36/64, where the formation the alkoxyl is relatively as aisresult of the cleavage of the cleavage of the ether bonds in the lactide, the EPR spectra of the irradiated samples exhibit spectrum bonds in the lactide, the EPR spectra of the irradiated samples exhibit spectrum very similar to the very similar to the radical [53,54]. hyperfine splitting EPR spectrum can be alkoxyl radical [53].alkoxyl The hyperfine splittingThe of the EPR spectrum canofbethe calculated by the following calculated by the following general formula: (2M 1 I 1 + 1) = number of the signals, where M the general formula: (2M1 I1 + 1) = number of the signals, where M is the number of the adjacent Hisatoms, number the 1adjacent H atoms, and I is spin 1 = ½ [54]. and I isofspin = 1/2 [54].

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(b) Figure 14. EPR spectra of diblock copolymers poly(TMC-b-DLA) (a) TMC/DLA 81/19 (b) TMC/DLA

Figure 14. irradiated EPR spectra of to diblock poly(TMC-b-DLA) TMC/DLA 81/19 (b) TMC/DLA 36/64 by EB dose ofcopolymers 30 kGy at dry ice temperature. (a)(a) Figure 14. EPR spectra of diblock copolymers poly(TMC-b-DLA) TMC/DLA 81/19 (b) TMC/DLA 36/64 irradiated by EB to dose of 30 kGy at dry ice temperature. 36/64 irradiated by EB to dose of 30 kGy at dry ice temperature. As expected, the EPR spectrum of the irradiated block copolymers TMC/DLA 36/64, exhibit singlet, which attributes to the acetyl radical, and a doublet, copolymers which can be assigned to the alkoxyl As As expected, expected, the the EPR EPRspectrum spectrumofofthe theirradiated irradiatedblock block copolymersTMC/DLA TMC/DLA36/64, 36/64, exhibit exhibit radical. It is well known that, similar to the peroxyl radical, alkoxyl radical EPR signals are relatively singlet, which attributes to the acetyl radical, and aa doublet, which can be assigned to the alkoxyl singlet, which attributes to the acetyl radical, and doublet, which can be assigned to the alkoxyl week, and very broad. Other contributing factor resides in the fact that alkoxyl radicals undergo radical. It well known that, to the radical, alkoxyl radical EPR are radical. It is isfast welldecay known that, similar similar the peroxyl peroxyl radical, alkoxyl radical EPR signals signals are relatively relatively relative via abstraction of to H-atoms from the neighboring chains producing hydroxide and week, and very broad. Other contributing factor resides in the fact that alkoxyl radicals undergo week, and very broad. Other contributing factor alkyl radicals as follows, as presented in Figure 15. resides in the fact that alkoxyl radicals undergo

relative relative fast fast decay decay via via abstraction abstraction of of H-atoms H-atoms from from the the neighboring neighboring chains chains producing producing hydroxide hydroxide and and alkyl radicals as follows, as presented in Figure 15. alkyl radicals as follows, as presented in Figure 15.

Figure 15. The abstraction of the H-atom from neighboring diblock copolymer poly(TMC-b-DLA) chains by the alkoxyl radical.

Figure 15. 15. The The abstraction abstraction of of the the H-atom H-atom from fromneighboring neighboringdiblock diblock copolymer copolymer poly(TMC-b-DLA) poly(TMC-b-DLA) Figure chains by the alkoxyl radical. chains by the alkoxyl radical.

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The EPR spectra of the irradiated TMC/DLA 81/19 are shown in Figure 14. Since the TMC content is very high, as mentioned, it is expected that the EPR spectrum present sextet for the alkyl radical in the TMC segment, similar to the free radical in polyethylene, in addition to the contribution from alkoxyl radicals. However, the spectrum, which was measured immediately after irradiation, exhibits a weak quadruplet, in addition to the singlet of the acetyl, and very weak doublet of the alkoxyl radical. The exhibit of the weak quadruplet rather than sextet may be contributed to the fast transformation of the TMC-located alkyl to allyl radicals [55,56]. Another contribution to the quadruplet may be the tertiary alkyl radical located at the PLA segment (which is known to be formed in PLA homopolymer [55]). The weakness of the quadruplet may also contribute to the fact that alkyl radical undergoes bimolecular crosslinking — as explained earlier, and disproportionation reactions. As also shown in Figure 15 the evidence of the crosslinking and disproportionation can be seen in the relatively fast disappearance of the quadruplet. It should also be mentioned that, as expected, the singlet of the acetyl radical stays relatively stable in comparison with the other free radicals. The relative stability of acetyl radical can clearly be explained by the presence of conjugated system. The presence of the carbonyl system C=O on the same C atom of the free radical provides an excellent conjugated system that decreases the density of the negativity leading to less reactive free radicals. However, the main factor of the stability of the acetyl and alkoxyl radicals is that they are in the DLA component, which is the crystal part of the TMC-DLA copolymer. Figure 16 shows the effects of the copolymers composition and the microstructure the on the immediate free radical concentration. As the DLA/TMC ratio increases, the immediate free radical concentration, in number of spin per gram, increases. This is clearly related to the content of ester linkages, since DLA contains in its chemical structure more ester groups than TMC, and to the increase in crystalline fraction. The overall decays of theses free radicals were monitored as a function of time and the DLA/TMC ratios. The inset in Figure 16 shows the second order decay of these radiolytically produced free radical — the predominant second order decay fits. It is very well accepted that in the absence of oxygen, the radiolytically produced alkyl radicals undergo second order crosslinking reactions [55]. It should also be mentioned that these observed second order decays may very well include pseudo-first order component from the abstraction of H atoms along the backbone of the chain by the alkoxyl radicals leading to the formation of alkyl radicals and hydroxide. This may explain the reason for some deviations from the straight lines of these second order fits (Figure 16). In the random copolymer a spectrum resembling that for PLA homopolymer was recorded (Figure 13). Since the random copolymer forms crystalline phase (as explained earlier [44]) it can contain trapped radicals at room temperature. Nevertheless, the number of radicals is relatively low (despite that the DLA mass content is 42%), lower than for block copolymer with only 19% DLA. Obviously the most stable radicals remain, and they decay slower than those in the block copolymer (Figure 16). Second order kinetics is predominant, but there may be still a fraction of faster decaying radicals since there is some initial deviation from the perfect second order fit. Those stable radicals may be diverse. H abstraction from methine groups located in the PLA units of the polymer chain creates tertiary alkyl radicals •C(CH3 )– (stable quartet) that, as in PLA homopolymer, decay slowly under vacuum because the carbonyl function assists in stabilization of the fragment [57]. Some relatively well stabilized allyl radicals may also be formed in the TMC units (see above) and contribute to the quartet signal. Alkoxyl and acetyl radicals, as the result of ester linkages scission, same as in block copolymers, are present as well. This corresponds well with the thermal characteristics of the irradiated samples, i.e., melting temperature of lactide crystallites was considerably decreasing with irradiation (Figure 9) that evidenced degradation of the DLA component.

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Figure 16. Free radical concentration and decay fitted to second order kinetics (inset) of diblock and Figure 16. Free radical concentration and decay fitted to second order kinetics (inset) of diblock and random copolymers irradiated by EB to a total dose of 30 kGy at dry ice temperature as measured at random copolymers irradiated by EB to a total dose of 30 kGy at dry ice temperature as measured at room temperature. Irradiation and measurement without under protective gas. room temperature. Irradiation and measurement without under protective gas.

4. 4. Conclusions Conclusions The results ofof this study demonstrate that thethe radiation chemistry ofof thethe trimethylene-lactide The results this study demonstrate that radiation chemistry trimethylene-lactide copolymers strongly depends onon thethe presence of of ester linkages, and therefore onon thethe TMC/DLA ratio copolymers strongly depends presence ester linkages, and therefore TMC/DLA ratio ofof this copolymer. It is concluded from the results of all techniques used in this study that as the ester this copolymer. It is concluded from the results of all techniques used in this study that as the ester group content increases, the probability of of copolymers degradation increases. inin copolymers group content increases, the probability copolymers degradation increases.Only Only copolymers with lowest ester linkage number, i.e., at the highest TMC content, the yield of crosslinking surpasses with lowest ester linkage number, i.e., at the highest TMC content, the yield of crosslinking the yield of scission, likewise in the carbonate homopolymers. surpasses the yield of scission, likewise in the carbonate homopolymers. EPR studies onon irradiated poly(TMC-b-DLA) block and random copolymers indicate the EPR studies irradiated poly(TMC-b-DLA) block and random copolymers indicatethat that the presence of amorphous polycarbonate units leads to the decrease of the radiolytic yield of radicals. presence of amorphous polycarbonate units leads to the decrease of the radiolytic yield of radicals. The complex EPREPR spectra showshow the production of alkoxyl and acetyl ester linkages The complex spectra the production of alkoxyl andradicals acetyl because radicalsofbecause of ester scission. Because ester linkages scission occurs in mostly crystalline region, since DLA formssince ordered linkages scission. Because ester linkages scission occurs in mostly crystalline region, DLA structure, as demonstrated by DSC experiments, one would expect the remarkable stability of both forms ordered structure, as demonstrated by DSC experiments, one would expect the remarkable alkoxyl andofthe acetyl radicals. the conjugated systemthe in conjugated the acetyl radical the stability both alkoxyl and In theaddition, acetyl radicals. In addition, systemenhances in the acetyl stability this radical. production of alkyl radicals at TMC segments expected, radicalofenhances the Moreover, stability ofthe this radical. Moreover, the production of alkyl were radicals at TMC which becomes the dominant reaction at high TMC content. However, the EPR spectra did not segments were expected, which becomes the dominant reaction at high TMC content. However, the show sextet did of the asof expected. the EPR spectra show quadruplet EPR aspectra notalkyl showradical a sextet the alkyl Instead, radical as expected. Instead, theweak EPR spectra show suggesting the formation of the the allylformation radicals inofthe and alkyl radicals the weak quadruplet suggesting theTMC allyl segments radicals in thetertiary TMC segments and in tertiary PLA units. Therefore, one can conclude that the initially formed secondary alkyl radicals in TMC alkyl radicals in the PLA units. Therefore, one can conclude that the initially formed secondary alkyl fragments fastundergo decay, e.g., recombination or crosslinking reactions andor unimolecular radicals undergo in TMCrelatively fragments relatively fast decay, e.g., recombination crosslinking transformation to allyl radicals. reactions and unimolecular transformation to allyl radicals. Radiation causes essentially nono significant changes the functional the copolymers, Radiation causes essentially significant changesinin the functionalgroups groupsofof the copolymers, especially at a relatively low dose as typically applied for sterilization. Even though the chemical especially at a relatively low dose as typically applied for sterilization. Even though the chemical composition is not altered, irradiation induces pronounced changes in the properties composition is not altered, irradiation induces pronounced changes in the propertiesofofthe the poly(TMC-co-DLA) of molecular molecular weight, weight,depending dependingon poly(TMC-co-DLA)copolymers copolymersdue duetotothe the increase increase or or decrease decrease of onthe themonomer monomerratio. ratio. Practical Practical implications implications may may be be that, that,through throughcopolymerizing copolymerizingthe thelactide lactidewith with TMC segments, it is possible not only to modify the properties of rigid PLA, but also to introduce TMC segments, it is possible not only to modify the properties of rigid PLA, but also to introduce certain resistance of this polymer against destructive action of ionizing radiation. certain resistance of radiation-degradable this radiation-degradable polymer against destructive action of ionizing radiation.

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Author Contributions: Conceptualization, R.A.W. and P.U.; Methodology, A.A.-W.; Investigation, A.A.-W., R.A.W., M.S. and Z.T.; Writing, A.A.-W., R.A.W., P.U. and M.A.-S.; Supervision, P.U., M.A.-S. and J.M.R.; Funding Acquisition, M.A.-S., A.A.-W. and P.U. Funding: This research was funded by National Science Center, Poland, grant No. 2012/05/N/ST5/01869 and by the IAEA grant No. POL/0/011 Upgrading the Capacities and Capabilities in Nuclear and Radiation Processing Technology and Applications by Increasing the Proficiency Level in National Nuclear Institutions. Acknowledgments: Authors thank Dr. S. Kadlubowski of Lodz University of Technology for his assistance in GPC measurements. Conflicts of Interest: The authors declare no conflict of interest.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13.

14. 15.

16. 17.

18.

Albertsson, A.-C.; Varma, I.K. Aliphatic Polyesters: Synthesis, Properties and Applications. Adv. Polym. Sci. 2002, 157, 1–40. Zhang, Z.; Grijpma, D.W.; Feijen, J. Triblock Copolymers Based on 1,3-Trimethylene Carbonate and Lactide as Biodegradable Thermoplastic Elastomers. Macromol. Chem. Phys. 2004, 205, 867–875. [CrossRef] Vert, M.; Li, S.M.; Speniehauer, G.; Guerir, P. Bioresorbability and biocomapatibility of aliphatic polyesters. J. Mater. Sci. Mater. M. 1992, 3, 43–46. [CrossRef] Södergård, A.; Stolt, M. Properties of lactic acid based polymers and their correlation with composition. Prog. Polym. Sci. 2002, 27, 1123–1163. [CrossRef] Drumright, B.R.E.; Gruber, P.R.; Henton, D.E. Polylactic Acid Technology. Adv. Mater. 2000, 12, 1841–1846. [CrossRef] Krikorian, V.; Pochan, D.J. Poly(l-Lactic Acid)/Layered Silicate Nanocomposite: Fabrication, Characterization, and Properties. Chem. Mater. 2003, 15, 4317–4324. [CrossRef] Hamad, K.; Kaseem, M.; Yang, H.W.; Deri, F.; Ko, Y.G. Properties and medical applications of polylactic acid: A review. eXPRESS Polym. Lett. 2015, 9, 435–455. [CrossRef] Nampoothiri, K.M.; Nair, N.R.; John, R.P. An overview of the recent developments in polylactide (PLA) research. Bioresour. Technol. 2010, 101, 8493–8501. [CrossRef] [PubMed] Liu, X.; Wang, T.; Chow, L.C.; Yang, M.; Mitchell, J.W. Effects of Inorganic Fillers on the Thermal and Mechanical Properties of Poly(lactic acid). Int. J. Polym. Sci. 2014, 827028. [CrossRef] [PubMed] Xu, X.; Yanga, Q.; Wang, Y.; Yu, H.; Chena, X.; Jing, X. Biodegradable electrospun poly(l-lactide) fibers containing antibacterial silver nanoparticles. Eur. Polym. J. 2006, 42, 2081–2087. [CrossRef] Yang, T.-C.; Hung, K.-C.; Wu, T.-L.; Wu, T.-M.; Wu, J.-H. A comparison of annealing process and nucleating agent (zinc phenylphosphonate) on the crystallization, viscoelasticity, and creep behavior of compression-molded poly(lactic acid) blends. Polym. Degrad. Stab. 2015, 121, 230–237. [CrossRef] Mathew, A.P.; Oksman, K.; Sain, M. Mechanical Properties of Biodegradable Composites from Poly Lactic Acid (PLA) and Microcrystalline Cellulose (MCC). J. Appl. Polym. Sci. 2005, 97, 2014–2025. [CrossRef] Pluta, M.; Paul, M.-A.; Alexandre, M.; Dubois, P. Plasticized Polylactide/Clay Nanocomposites. II. The Effect of Aging on Structure and Properties in Relation to the Filler Content and the Nature of its Organo-Modification. J. Polym. Sci. Part B 2006, 44, 312–325. [CrossRef] Yang, S.; Wu, Z.-H.; Yang, W.; Yang, M.-B. Thermal and mechanical properties of chemical crosslinked polylactide (PLA). Polym. Test. 2008, 27, 957–963. [CrossRef] Quynh, T.M.; Mitomo, H.; Nagasawa, N.; Wada, Y.; Yoshii, F.; Tamada, M. Properties of crosslinked polylactides (PLLA & PDLA) by radiation and its biodegradability. Eur. Polym. J. 2007, 43, 1779–1785. [CrossRef] Zhang, Z.; Kuijer, R.; Bulstra, S.K.; Grijpma, D.W.; Feijen, J. The in vivo and in vitro degradation behavior of poly(trimethylene carbonate). Biomaterials 2006, 27, 1741–1748. [CrossRef] [PubMed] Habraken, W.J.; Zhang, Z.; Wolke, J.G.; Grijpma, D.W.; Mikos, A.G.; Feijen, J.; Jansen, J.A. Introduction of enzymatically degradable poly(trimethylene carbonate) microspheres into an injectable calcium phosphate cement. Biomaterials 2008, 29, 2464–2476. [CrossRef] [PubMed] Feng, J.; Zhuo, R.-X.; Zhang, X.-Z. Construction of functional aliphatic polycarbonates for biomedical applications. Prog. Polym. Sci. 2012, 37, 211–236. [CrossRef]

Polymers 2018, 10, 672

19. 20.

21. 22.

23.

24.

25.

26. 27. 28. 29. 30.

31. 32. 33. 34.

35. 36.

37.

38.

39.

20 of 21

Ruckenstein, E.; Yuan, Y. Molten Ring-Open Copolymerization of l-Lactideand Cyclic Trimethylene Carbonate. J. Appl. Polym. Sci. 1998, 69, 1429–1434. [CrossRef] Pêgo, A.P.; Poot, A.A.; Grijpma, D.W.; Feijen, J. Copolymers of trimethylene carbonate and epsilon-caprolactone for porous nerve guides: Synthesis and properties. J. Biomater. Sci. Polym. Ed. 2001, 12, 35–53. [CrossRef] [PubMed] Jie, C.; Zhu, K.J.; Shilin, Y. Preparation, characterization and biodegradable characteristics of poly(1,3-trimethylene carbonate-co-glycolide). Polym. Int. 1996, 41, 369–375. [CrossRef] Han, Y.; Fan, Z.; Lu, Z.; Zhang, Y.; Li, S. In vitro degradation of poly[(l-lactide)-co(trimethylene carbonate)] copolymers and a composite with poly[(l-lactide)-co-glycolide] fibers as cardiovascular stent material. Macromol. Mater. Eng. 2012, 297, 128–135. [CrossRef] Zhu, K.J.; Zhang, J.X.; Wang, C.; Yasuda, H.; Ichimaru, A.; Yamamoto, K. Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres based on poly(l-lactide) and its carbonate copolymers. J. Microencapsul. 2003, 20, 731–743. [CrossRef] [PubMed] Yang, J.; Liu, F.; Tu, S.; Chen, Y.; Luo, X.; Lu, Z.; Wei, J.; Li, S. Haemo- and cytocompatibility of bioresorbable homo- and copolymers prepared from 1,3-trimethylene carbonate, lactides, and e-caprolactone. J. Biomed. Mater. Res. A 2010, 94, 396–407. [CrossRef] Pego, A.P.; Van Luyn, M.J.A.; Brouwer, L.A.; Van Wachem, P.B.; Poot, A.A.; Grijpma, D.W.; Feijen, J. In vivo behavior of poly(1,3-trimethylene carbonate) and copolymers of 1,3-trimethylene carbonate with D,L-lactide or ∈-caprolactone: Degradation and tissue response. J. Biomed. Mater. Res. 2003, 67A, 1044–1054. [CrossRef] [PubMed] Savaris, M.; dos Santos, V.; Brandalise, R.N. Influence of different sterilization processes on the properties of commercial poly(lactic acid). Mater. Sci. Eng. C 2016, 69, 661–667. [CrossRef] [PubMed] Dempsey, D.J.; Thirucote, R.R. Sterilization of medical devices: A review. J. Biomater. Appl. 1989, 3, 454–523. [CrossRef] [PubMed] Weir, N.A.; Buchanan, F.J.; Orr, J.F.; Farrar, D.F.; Boyd, A. Processing, annealing and sterilisation of poly-l-lactide. Biomaterials 2004, 25, 3939–3949. [CrossRef] [PubMed] Melski, K.; Kubera, H.; Głuszewski, W.; Zimek, Z. Effect of ionizing radiation on the properties of PLA packaging materials. Nukleonika 2011, 56, 65–69. Mansouri, M.; Berrayah, A.; Beyens, C.; Rosenauer, C.; Jama, C.; Maschke, U. Effects of electron beam irradiation on thermal and mechanical properties of poly(lactic acid) films. Polym. Degrad. Stab. 2016, 133, 293–302. [CrossRef] Leonard, D.J.; Pick, L.T.; Farrar, D.F.; Dickson, G.R.; Orr, J.F.; Buchanan, F.J. The modification of PLA and PLGA using electron-beam radiation. J. Biomed. Mater. Res. Part A 2009, 89A, 567–574. [CrossRef] [PubMed] Chakoli, A.N.; He, J.; Chayjan, M.A.; Huang, Y.; Zhang, B. Irradiation of poly(l-lactide) biopolymer reinforced with functionalized MWCNTs. RSC Adv. 2015, 5, 55544–55549. [CrossRef] Chapiro, A.; Tabata, Y.; Charlesby, A.; Stannett, V.; Dole, M.; Dobo, J. Future of radiation processing of polymers. Radiat. Phys. Chem. 1990, 35, 15–17. O’Donnell, J.H. Radiation chemistry of polymers. In The Effects of Radiation on High-Technology Polymers; Reichmanis, E., O’Donnell, J.H., Eds.; ACS Symposium Series 381; American Chemical Society: Washington, DC, USA, 1989. Gupta, M.C.; Deshmukh, V.G. Radiation effects on poly(lactic acid). Polymer 1983, 24, 827–830. [CrossRef] Rytlewski, P.; Malinowski, R.; Moraczewski, K.; Zenkiewicz, M. Influence of some crosslinking agents on thermal and mechanical properties of electron beam irradiated polylactide. Radiat. Phys. Chem. 2010, 79, 1052–1057. [CrossRef] Jozwiakowska, J.; Wach, R.A.; Rokita, B.; Ulanski, P.; Nalawade, S.P.; Grijpma, D.W.; Feijen, J.; Rosiak, J.M. Influence of electron beam irradiation on physicochemical properties of poly(trimethylene carbonate). Polym. Degrad. Stab. 2011, 96, 1430–1437. [CrossRef] Miao, P.; Zhao, C.; Xu, G.; Fu, Q.; Tang, W.; Zeng, K.; Wang, Y.; Zhou, H.; Yang, G. Degradation of Poly(d,l-lactic acid)-b-poly(ethyleneglycol)-b-poly(d,l-lactic acid) Copolymer by Electron Beam Radiation. J. Appl. Polym. Sci. 2009, 112, 2981–2987. [CrossRef] Calıs, S.; Bozdag, S.; Kas, H.S.; Tuncay, M.; Hıncal, A.A. Influence of irradiation sterilization on poly(lactide-co-glycolide) microspheres containing anti-inflammatory drugs. II Farmaco 2002, 57, 55–62. [CrossRef]

Polymers 2018, 10, 672

40. 41. 42. 43. 44. 45. 46. 47. 48.

49. 50. 51. 52.

53. 54. 55. 56. 57.

21 of 21

Loo, S.C.J.; Ooi, C.P.; Boey, F.Y.C. Radiation effects on poly(lactide-co-glycolide) (PLGA) and poly(l-lactide) (PLLA). Polym. Degrad. Stab. 2004, 83, 259–265. [CrossRef] Kowalski, A.; Libiszowski, J.; Duda, A.; Penczek, S. Polymerization of l,l-Dilactide Initiated by Tin(II) Butoxide. Macromolecules 2000, 33, 1964–1971. [CrossRef] Duda, A.; Penczek, S. On the difference of reactivities of various aggregated forms of aluminum isopropoxide in initiating ring-opening polymerizations. Macromol. Rapid Commun. 1995, 16, 67–76. [CrossRef] Bernardo, K.D.S.; Robert, A.; Dahan, F.; Meunier, B. Preparation of new chiral Schiff base ligands containing a binaphthyl moiety. X-ray structure of the H2Cl4 Salbinapht ligand. New J. Chem. 1995, 19, 129–131. Socka, M.; Duda, A.; Adamus, A.; Wach, R.A.; Ulanski, P. Lactide/trimethylene carbonate triblock copolymers: Controlled sequential polymerization and properties. Polymer 2016, 87, 50–63. [CrossRef] Fischer, E.W.; Sterzel, H.J.; Wegner, G. Investigation of the structure of solution grown crystals of lactide copolymers by means of chemical reactions. Colloid. Polym. Sci. 1973, 251, 980–990. [CrossRef] Eaton, G.R.; Eaton, S.S.; Barr, D.P.; Weber, R.T. Quantitative EPR; Springer: New York, NY, USA, 2010; ISBN 978-3-211-92947. ˙ Pamuła, E.; Błazewicz, M.; Paluszkiewicz, C.; Dobrzynski, ´ P. FTIR study of degradation products of aliphatic polyesters–carbon fibres composites. J. Mol. Struct. 2001, 596, 69–75. [CrossRef] Jia, Y.T.; Kim, H.Y.; Gong, J.; Lee, D.R.; Ding, B.; Bhattarai, N. Synthesis and degradation of PLA–PCL–PLA triblock copolymer prepared by successive polymerization of ε-caprolactone and dl-lactide. Polym. Int. 2004, 53, 312–319. [CrossRef] Charlesby, A. Atomic Radiation and Polymers; Pergamon Press: Oxford, UK, 1960. Moad, C.L.; Winzor, D.J. Quantitative characterization of radiation degradation in polymers by evaluation of scission and cross-linking yields. Prog. Polym. Sci. 1998, 23, 759–813. [CrossRef] Solarski, S.; Ferreira, M.; Devaux, E. Characterization of the thermal properties of PLA fibers by modulated differential scanning calorimetry. Polymer 2005, 46, 11187–11192. [CrossRef] Liu, Y.; Sun, J.; Bian, X.; Feng, L.; Xiang, S.; Sun, B.; Chen, Z.; Li, G.; Chen, X. Melt stereocomplexation from poly(l-lactic acid) and poly(d-lactic acid) with different optical purity. Polym. Degrad. Stab. 2013, 98, 844–852. [CrossRef] ˙ formed in irradiated single crystals of rhamnose. Samskog, P.-O.; Lund, A. The alkoxy radical RCHO Chem. Phys. Lett. 1980, 75, 525–527. [CrossRef] Rieger, R.H. Electron Spin Resonance-Analysis and Interpretation; Royal Society of Chemistry: Cambridge, UK, 2007; ISBN 978-0-85404-355-3. Barbanalbandi, A.; Hill, D.J.T.; O’Donnel, J.; Pomery, P.; Whittaker, A. An electron spin resonance study on g irradiated poly(l-lactic acid) and poly(dl-lactic acid). Polym. Degrad. Stab. 1995, 50, 297–304. [CrossRef] Kasser, M.J.; Silverman, J.; Al-Sheikhly, M. EPR Simulation of Polyenyl Radicals in Ultrahigh Molecular Weight Polyethylene. Macromolecules 2010, 43, 8862–8867. [CrossRef] Kasser, M.J.; Silverman, J.; Al-Sheikhly, M. On the Mechanism of Polyenyl Photoconversion in Irradiated Ultrahigh Molecular Weight Polyethylene. Macromolecules 2010, 43, 8868–8873. [CrossRef] © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).