Strong Disturbance Effect of Comonomer Units with Opposite

The random copolymers of optically active l-lactic acid (LLA) and d-2-hydroxybutanoic acid (d-2HB) [P(LLA-co-d-2HB)s] with the opposite configurations...
1 downloads 0 Views 3MB Size
Download PDF
Article Cite This: Cryst. Growth Des. XXXX, XXX, XXX−XXX

pubs.acs.org/crystal

Strong Disturbance Effect of Comonomer Units with Opposite Configuration on Crystallization of Optically Active Monomer-Based Random Copolymers Hideto Tsuji,* Soma Noda, Yuki Arakawa, and Tadashi Sobue Department of Environmental and Life Sciences, Graduate School of Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan

Downloaded via UNIV OF SOUTH DAKOTA on September 9, 2018 at 20:59:30 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: The random copolymers of optically active L-lactic acid (LLA) and D2-hydroxybutanoic acid (D-2HB) [P(LLA-co-D-2HB)s] with the opposite configurations and 2-hydroxybutanoic acid (2HB) unit content range of 0−100 mol % were synthesized by polycondensation, and their crystallization behavior was compared with that reported for the random copolymers composed of optically active L-lactic acid and L-2-hydroxybutanoic acid (L-2HB) [P(LLA-co-L-2HB)s] with identical configurations. P(LLA-co-D-2HB) copolymers were crystallizable at 2HB unit contents only around 0 and 100 mol % (i.e., 0−11 and 95−100 mol %), in marked contrast with the result reported for the P(LLA-co-L-2HB)s with the identical configurations crystallizable at all 2HB contents from 0 to 100 mol %. It was reported for the first time that the disturbance effect of minor monomer units with the configuration opposite to that of the major monomer units on the crystallization of the random copolymers is much stronger than that of the minor monomer units with the configuration identical to that of the major monomer units. Wide-angle X-ray diffractometry results strongly suggested that the minor monomer units were excluded from the crystalline regions of the major monomer units when two types of monomers have the opposite configurations, although the minor monomer units are reported to be incorporated in the crystalline regions of the major monomer units when two types of monomers have identical configurations. Differential scanning calorimetry results revealed that the segmental mobility of the melt-quenched P(LLA-co-D-2HB) samples composed of the monomers with the opposite configurations is much higher than that of the melt-quenched P(LLA-co-L-2HB) samples composed of the monomers with identical configurations. (LLA-co-L-2HB)] (Figure 1)11,12 and poly(D-lactic acid-co-D-2hydroxybutanoic acid) [P(DLA-co-D-2HB)]12,13 for the 2hydroxybutanoic acid (2HB) unit content range of 0−100 mol %, 11,13 poly( L -lactic acid-co-glycolic acid) [P(LLA-coGA)]14−18 for the lactic acid (LA) unit content ranges of 0− 20 mol % and 73−100 mol %,18 and poly(D-2-hydroxy-3methylbutanoic acid-co-D-2-hydroxybutanoic acid) [P(D2H3MB-co-D-2HB)] at the 2HB unit content of approximately 50 mol %.19 The last example of cocrystallizability of P(D2H3MB-co-D-2HB) at approximately 50 mol % strongly suggests that this copolymer should be crystallizable, and two types of the monomer units should cocrystallize in the same lattice for all the monomer unit content range of 0−100 mol %. Marubayashi et al. reported that L-lactic acid (LLA) units and some relatively small-sized 2-hydroxyalkanoic acid comonomer units of LLA-rich random copolymers such as optically inactive glycolic acid and 2-hydroxyisobutanoic acid (2-hydroxy-2-methylpropanoic acid), and optically active L-2hydroxy-3-methylbutanoic acid cocrystallize in the same lattice,

1. INTRODUCTION Optically active 2-hydroxyalkanoic acid- or α-hydroxyalkanoic acid-based polymers including poly(L-lactic acid) (PLLA) or poly(L-2-hydroxypropanoic acid) can be utilized in biomedical, pharmaceutical, environmental applications because they are biodegradable and biocompatible.1−10 PLLA has attracted much attention due to its mechanical properties suitable for a wide range of commodity articles and producibility from starch- and sugar-based renewable plant resources such as corn, sugar cane, tubers, and roots.1−10 In previous papers, the cocrystallization of two types of monomer units or their incorporation in the same crystalline lattice is reported for optically active 2-hydroxyalkanoic acidbased random copolymers, despite the energetic disadvantage of random incorporation of two different types of monomers with different chemical structures or different types of side chains compared to the crystallization in homopolymers.11−19 The cocrystallization of different types of monomer units can be monitored by the crystalline peak angle shifts in wide-angle X-ray diffractometry (WAXD) upon altering the minor monomer unit content. The reported examples for optically active 2-hydroxyalkanoic acid-based random copolymers include poly(L-lactic acid-co-L-2-hydroxybutanoic acid) [P© XXXX American Chemical Society

Received: July 5, 2018 Revised: August 15, 2018 Published: August 15, 2018 A

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

The aforementioned optically active 2-hydroxyalkanoic acidbased random copolymers consist of the two optically active monomers with the identical configurations or of one optically active and one optically inactive monomers. Another type of optically active 2-hydroxyalkanoic acid-based random copolymers are composed of two optically active monomers with the opposite configurations. Poly(L-lactic acid-co-D-lactic acid) [P(LLA-co-DLA)], poly(L-lactide-co-D-lactide), and poly(Llactide-co-meso-lactide) random copolymers are comprised of monomers with the identical chemical structures and opposite configurations and lose the crystallizability upon approaching a 50/50 monomer unit ratio,22,23 except for crystallizable syndiotactic PLA, i.e., poly(L-lactic acid-alt-D-lactic acid).24,25 However, detailed studies of the crystallization behavior of optically active 2-hydroxyalkanoic acid-based random copolymers composed of two optically active monomers with the different chemical structures and opposite configurations and the disturbance effect of minor monomer units with the configuration opposite to that of major monomer units on crystallization have not been reported so far. For the alternating copolymers of optically active 2-hydroxyalkanoic acid and 3-hydroxyalkanoic acid, the crystallization and melting temperature (Tm ) values are reported for alternating copolymers (not random copolymers) of poly(D-2-hydroxybutanoic acid-alt-D-3-hydroxybutanoic acid) [P(D-2HB-alt-D3HB)] and poly(L-2-hydroxybutanoic acid-alt-D-3-hydroxybutanoic acid) [P(L-2HB-alt-D-3HB)].26 The former and latter alternating copolymers comprised two optically active monomers with the identical configurations and the opposite configurations, respectively. Both alternating copolymers were crystallizable, and, interestingly, Tm values were much higher for the alternating copolymer composed of the monomers of the identical configurations (233 °C) than for the alternating copolymer composed of the monomers of the opposite configurations (83 °C).26 In the present study, optically active 2-hydroxyalkanoic acidbased random copolymers composed of two optically active monomers with the different chemical structures and opposite configurations, i.e., poly(L-lactic acid-co-D-2-hydroxybutanoic acid) [P(LLA-co-D-2HB)] (Figure 1) with a wide 2hydroxybutanoic acid (2HB) unit content range of 0−100 mol %. The effect of incorporated minor monomer units with the different chemical structure and opposite configuration on the crystallization of the random copolymers were investigated, and the obtained results were compared with those reported for optically active 2-hydroxyalkanoic acid-based random copolymers composed of monomer units with the different chemical structures and identical configurations, i.e., P(LLA-co11 L-2HB). The comparison between the present and reported results elucidated the strong disturbance effect of minor monomer units with the different chemical structure and opposite configuration on the crystallization.

Figure 1. Molecular structures of P(LLA-co-D-2HB) and P(LLA-co-L2HB).

whereas relatively large-sized optically active L-2-hydroxy-4methylpentanoic acid units in LLA-rich random copolymers were excluded from LLA unit crystalline regions.16 Poly(Llactic acid-co-L-phenyllactic acid)s were crystallizable for LA unit contents of 94−100 mol % during solvent evaporation.20 Considering the narrow crystallizable range, the minor monomer units of relatively large-sized L-phenyllactic acid units should be excluded from the LLA unit crystalline regions. In addition, the cocrystallization of two types of monomer units are reported for random copolymers of optically active 2hydroxyalkanoic acid and 2-amino acid (or α-amino acid), poly(L-lactic acid-co-L-alanine) [P(LLA-co-LAL)], and poly(Dlactic acid-co-D-alanine) [P(DLA-co-DAL)] for the alanine unit contents up to 12 or 13 mol %.21 It is interesting to note that the incorporation and exclusion of comonomer units in the crystalline lattice depends on the crystallization method.21 That is, the alanine units as minor monomer units of the meltcrystallized P(LLA-co-LAL) or P(DLA-co-DAL) random copolymers was incorporated into the LLA or D-lactic acid unit crystalline regions, whereas the those of the solutioncrystallized P(LLA-co-LAL) or P(DLA-co-DAL) random copolymers were excluded from the LLA or D-lactic acid unit crystalline regions.21 The cocrystallization of four types of monomer units can occur in the case of stereocomplex (SC) crystallization between optically active L- and D-configured 2-hydroxyalkanoic acid-based random copolymers12,19 and L- and D-configured random copolymers of 2-hydroxyalkanoic acid and 2-amino acid.21 The reported examples are symmetry P(LLA-co-L2HB)(56/44)/P(DLA-co-D-2HB)(52/48) blends,12 staggered asymmetry P(LLA-co- L -2HB)(50/50)/P( D -2H3MB-co- D 2HB)(50/50) blends,19 and symmetry P(LLA-co-LAL)/P(DLA-co-DAL) blends with alanine unit contents up to 13 mol %.21 Here, symmetry and asymmetry mean that the copolymers with the opposite configurations are composed of the monomers with the identical and different chemical structures, respectively. Interestingly again, the incorporation of the comonomer units in the same crystalline lattice or not depends on the crystallization method. For P(LLA-co-LAL) and P(DLA-co-DAL), in contrast with nonblended random copolymer samples, the alanine units as minor monomer units of solution-crystallized blends were incorporated in SC crystalline regions, whereas those of melt-crystallized blends were excluded from SC crystalline regions.21

2. EXPERIMENTAL SECTION 2.1. Materials. PLLA, poly(D-2-hydroxybutanoic acid) [P(D2HB)], and P(LLA-co-D-2HB) polymers was synthesized by polycondensation of LLA and D-2-hydroxybutanoic acid [(R)-2hydroxybutyric acid] (≥98.0%, Sigma-Aldrich Co., Tokyo, Japan) using 5 wt % p-toluenesulfonic acid (monohydrate, guaranteed grade, Nacalai Tesque Inc., Kyoto, Japan) as the catalyst, as reported previously.11 The reaction was performed with 1 g of monomer(s) at 130 °C under a nitrogen atmosphere and atmospheric pressure for 5 h and then under reduced pressure, i.e., 1.5 kPa for 6 h for PLLA, 5.2 kPa for 14 h for P(D-2HB), and 2.3−5.4 kPa for 14 h for P(LLA-co-DB

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

Table 1. Molecular Characteristics of Polymers Used in the Present Study D-2HB

code P(D-2HB) HB95 HB87 HB75 HB52 HB27 HB21 HB16 HB11 HB6 PLLA

in the feed (mol %) 100.0 95.1 89.7 75.0 50.8 25.6 20.5 15.4 10.3 5.2 0.0

D-2HB

unit content in polymera (mol %)

D-2HB

100.0 95.2 87.3 74.5 51.6 27.0 21.3 16.3 11.0 5.8 0.0

unit content in polymera (wt %) 100.0 96.4 90.2 79.6 58.7 33.0 26.5 20.6 14.1 7.6 0.0

Mnb (g mol−1)

Mw/Mnb

[α]25589c

× × × × × × × × × × ×

1.7 2.8 2.2 2.6 2.4 3.3 2.0 2.2 2.3 2.6 2.7

116.7 108.8 95.7 63.6 5.9 −64.8 −83.2 −99.0 −118.8 −134.1 −151.5

1.0 9.1 1.2 9.4 9.6 5.9 1.4 1.0 1.1 1.0 9.5

4

10 103 104 103 103 103 104 104 104 104 103

a

Estimated by 1H NMR. bMn and Mw are number- and weight-average molecular weights, respectively. cMeasured in chloroform. rate of 10 °C min−1. WAXD measurements were carried out at 25°C using a RINT-2500 (Rigaku Co., Tokyo, Japan) equipped with a Cu− Kα source (λ = 1.5418 Å).11

2HB) copolymers with LLA/D-2HB = 5/95−25/75 in the feeds and for 24 h for P(LLA-co-D-2HB) copolymers with LLA/D-2HB = 50/ 50−95/5 in the feeds.11 LLA used for the synthesis of PLLA and P(LLA-co-D-2HB) copolymers was prepared by hydrolytic degradation of L-lactide (assay 99.5% Purac Biochem, Gorinchem, The Netherlands) with distillated water [L-lactide/water (mol/mol) = 1/ 2] at 98 °C for 30 min.11 The synthesized PLLA, P(D-2HB), and P(LLA-co-D-2HB) copolymers (LLA/D-2HB = 80/20−95/5 in the feeds) were purified by reprecipitation using chloroform and methanol (both guaranteed grade, Nacalai Tesque Inc.) as the solvent and nonsolvent, respectively,27 whereas P(LLA-co-D-2HB) copolymers (LLA/D-2HB = 5/95−75/25 in the feeds) were purified by repeated extraction with methanol (guaranteed grade, Nacalai Tesque Inc.) (30 mL). The purified polymers were dried under reduced pressure for at least 6 days. Thus-purified samples are “purified samples”.11 The melt-quenching of the purified samples sealed in test tubes under reduced pressure was performed by melting at 190 °C for 3 min and subsequent quenching at 0 °C for at least 5 min. Thus-prepared samples are “melt-quenched samples”.11 The crystallization of “meltquenched samples” sealed in test tubes under reduced pressure was carried out by annealing at a crystallization temperature (Tc) for 24 h and then they were quenched at 0 °C for at least 5 min to stop further crystallization.11 Thus-prepared samples are “melt-quenched-crystallized samples”. Here, the quenching process was added to the conventional melt-crystallization process,11 because the quenching process before crystallization is known to increase the crystalline nuclei, resulting in accelerated crystallization, which is favorable for the samples with low crystallizability to investigate the crystallizability.28 2.2. Physical Measurements and Observation. The weightand number-averaged molecular weights (Mw and Mn, respectively) of the purified polymers were estimated in chloroform at 40 °C using a Tosoh (Tokyo, Japan) GPC system with two TSK gel columns (GMHXL) and polystyrene standards.11 The [α]25589 of the polymers was obtained in chloroform at a concentration of 1 g dL−1 and 25 °C using a JASCO (Tokyo, Japan) P-2100 polarimeter at a wavelength of 589 nm.11 The monomer contents and sequences of synthesized P(LLA-co-D-2HB) copolymers were evaluated from the 1H and 13C NMR spectra measured in deuterated chloroform (50 mg mL−1) by a Bruker BioSpin (Kanagawa, Japan) AVANCE III 400 using tetramethylsilane as the internal standard.11 The molecular characteristics of the polymers used in the present study are shown in Table 1. In the table, the P(LLA-co-D-2HB) copolymers are abbreviated as HBX wherein X exhibits the mol % of D-2HB in the copolymer.11 The glass transition, cold crystallization, and melting temperatures (Tg, Tcc, and Tm, respectively) and the enthalpies of cold crystallization and melting (ΔHcc and ΔHm, respectively) were determined with a Shimadzu (Kyoto, Japan) DSC-50 differential scanning calorimeter under a nitrogen gas flow at a rate of 50 mL min−1.11 The samples (ca. 3 mg) were heated from 0 to 200°C at a

3. RESULTS AND DISCUSSION 3.1. Monomer Compositions and Sequences of P(LLA-co-D-2HB) Copolymers. To estimate the content and sequence of monomer units of the P(LLA-co-D-2HB) copolymers, 1H and 13C NMR measurements were carried out. Figure 2 shows the typical 1H spectra and 13C NMR spectra of carbonyl carbon for the P(LLA-co-D-2HB) copolymer with 2hydroxybutanoic acid (2HB) unit content of 52 mol % (HB52) and those reported for the P(LLA-co-L-2HB) copolymer with 2HB unit content of 44 mol %,11 together with the molecular structure of poly(lactic acid-co-2-hydroxybutanoic acid). The 1H NMR peaks of spectra for P(LLA-coL-2HB) at approximately 5.2 and 1.6 ppm are attributed to correspondingly methine and methyl protons of LA units and those at approximately 5.1, 2.0, and 1.0 are ascribed to respectively methine, methylene, and methyl protons of 2HB units. Although probably due to the difference in enantiomeric form of 2HB, the peak shapes of the P(LLA-co-D-2HB) copolymer are different from those of the P(LLA-co-L-2HB) copolymer, and each peak of the P(LLA-co-D-2HB) copolymer was broader than that of the P(LLA-co-L-2HB) copolymer, but the chemical shift value of each peak is quite similar. 2HB unit contents were evaluated based on the ascription and area of the peaks, and the estimated 2HB unit contents are summarized in Table 1. As seen in this table, 2HB unit contents in the copolymers are very similar to those in the feeds, which is typical for the copolymers synthesized by polycondensation such as P(LLA-co-GA)18 and confirms the incorporation of both types of monomer units in the copolymers. 13 C NMR spectra of carbonyl carbon for P(L-2HB), P(LLAco-L-2HB) copolymer with 2HB unit content of 44 mol %, and PLLA reported in the previous paper are shown in Figure S1 for reference.11 The 13C NMR peaks of the P(LLA-co-L-2HB) copolymer at approximately 169.6 and 169.1 ppm are assigned to the carbonyl carbons of the LLA unit neighboring an LLA unit (LLA−LLA) and the L-2HB unit neighboring an 2HB unit (L-2HB-L-2HB), respectively, and the peaks at 169.8 and 168.9 ppm are attributed to the carbonyl carbons of the LLA unit neighboring an L-2HB unit (LLA-L-2HB) and the L-2HB unit neighboring an LLA unit (L-2HB-LLA), respectively.11 In the expressions of monomer sequence such as LLA-LLA, the ester group direction between the two monomer units is −CO-OC

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

3.2. Wide-Angle X-ray Diffractometry. To investigate the crystalline structure, interplanar distance (d), and crystallinity (Xc) of the P(LLA-co-D-2HB) samples, WAXD measurements were performed. Figure 3 shows the WAXD profiles of the purified and melt-quenched-crystallized P(LLAco-D-2HB) samples, together with those reported for the purified and melt-crystallized P(LLA-co-L-2HB) samples.11 The magnified figure of PLLA, HB6, and HB11 are shown in Figure S2. Both the purified and melt-quenched-crystallized PLLA samples had main crystalline diffractions at approximately 17 and 19° specific to (110)/(200) and (113)/(203) planes, respectively, of α- and δ- (or α′-)forms, and only purified PLLA sample had crystalline small peaks at approximately 12.5, 15, and 22.5° specific only to αform,11,18,29−34 which are shown with arrows in Figures 3 and S2. These results indicate that PLLA crystallized in α- and δ-(α′-)forms during precipitation and crystallization at 70 °C, respectively, in agreement with the reported results.11 On the other hand, both the purified and melt-quenched-crystallized P(D-2HB) samples showed the main crystalline diffraction peaks at approximately 15 and 17°, consistent with the reported values.35,36 In marked contrast with the P(LLA-co-L2HB) [Figure 3c,d]11 or P(DLA-co-D-2HB)13 copolymers composed of the monomers with identical configurations, which are crystallizable in the 2HB unit content range from 0 to 100 mol %, the P(LLA-co-D-2HB) copolymers composed of the monomers with the opposite configurations were crystallizable in the narrow 2HB unit content ranges of 0−11 and 95−100 mol % for precipitation and 0−6 and 100 mol % for the melt-quenching crystallization. This result is indicative of the fact that comonomer with the opposite configuration has a strong disturbance effect on the crystallization of random copolymers composed of the optically active monomers and reduced the crystallizable 2HB unit content range of the P(LLA-co-D-2HB) copolymers. For the LLA-rich P(LLA-co-D2HB) copolymers, in addition to main crystalline diffraction at approximately 17 and 19°, the purified HB6 and HB11 samples and the melt-quenched-crystallized HB6 samples had crystalline diffractions specific only to the α-form (Figure S2), indicating that these samples crystallized in α-form. It is interesting to note that in the case of the melt-quenchedcrystallized, the crystalline form changed from δ- (or α′-) form for PLLA to α-form for HB6. For the D-2HB-rich P(LLA-co-D2HB) copolymers, the purified HB95 had crystalline diffraction, which is similar to those of the purified and meltquenched-crystallized P(D-2HB) samples. On the other hand, Pan et al. reported that the transition from δ- (or α′-) form to α-form occurs in PLLA at Tc below 110 °C by incorporation of poly(DL-lactide).33 The d values of the purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples were evaluated from the WAXD profiles shown in Figure 3. The obtained d values are summarized in Table S1 and plotted in Figure 4a as a function of 2HB unit content. The d values of the purified P(D-2HB) sample at 2θ = 14.80 and 17.36° were 5.99 and 5.11 Å, respectively, whereas those of the melt-quenched-crystallized P(D-2HB) sample at 2θ = 14.78 and 17.30° were 5.99 and 5.13 Å, respectively, indicating that the crystallization method did not alter d values. The d values of the purified HB95 sample at 2θ = 14.80 and 17.34° were 5.99 and 5.11 Å, respectively. These d values are in complete agreement with those of the purified P(D-2HB) sample, exhibiting the incorporation of 5 mol % of LLA units with the configuration opposite to D-2HB

Figure 2. 1H NMR spectra (a) and 13C NMR spectra of carbonyl carbon (b) for P(LLA-co-D-2HB) with 2HB unit content of 52 mol % (HB52) and those reported for P(LLA-co-L-2HB) with 2HB unit content of 44 mol %, together with molecular structure of poly(lactic acid-co-2-hydroxybutanoic acid). The dashed and dotted lines are 13C NMR chemical shift values of monomer sequences, LLA-LLA and L2HB-L-2HB, respectively. The spectra for P(LLA-co-L-2HB) with 2HB unit content of 44 mol % were reproduced from ref 11 with permission from Polymer. Copyright (2015) Elsevier.

not -O−CO-. In contrast, the 13C NMR peak of the P(LLA-coD-2HB) copolymer was broad in the range of 169.7−168.3 and composed of multiple peaks with low separation. Similar to the 1 H NMR spectra, such a broad peak of the P(LLA-co-D-2HB) copolymer should be caused by the combination of the monomers having the opposite configurations. In the case of the P(LLA-co-L-2HB) copolymer composed of the monomers with the identical configurations, the chemical shift of each peak is determined by only two monomer sequences.11 If the chemical shifts of the peaks for the P(LLA-co-D-2HB) copolymer are determined by only two monomer sequences, four peaks should appear as in the case of the P(LLA-co-L2HB) copolymer. Therefore, the peak shape and separation of the P(LLA-co-D-2HB) copolymer indicate that the chemical shifts of the peaks are determined by the monomer sequence longer than two units. Also, it should be noted that the differences in molecular weight and its distribution between P(LLA-co-D-2HB) (Mn = 9.6 × 103 g mol−1 and Mw/Mn = 2.4) and P(LLA-co-L-2HB) (Mn = 1.4 × 104 g mol−1 and Mw/Mn = 1.3) may affect the shape and chemical shifts of 13C NMR spectra. On the other hand, if the P(LLA-co-D-2HB) copolymer has a blocky structure, only two independent peaks identical to those of PLLA and P(D-2HB) should have appeared. Considering the aforementioned results strongly suggest the P(LLA-co-D-2HB) copolymer has relatively random monomer unit distribution. D

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

Figure 3. WAXD profiles of purified (a) and melt-quenched-crystallized (b) P(LLA-co-D-2HB) samples, purified (c) and melt-crystallized (d) P(LLA-co-L-2HB) samples. The dashed and dotted lines are the crystalline diffraction angles of P(D-2HB) or P(L-2HB) and PLLA, respectively. The arrows indicate the crystalline diffractions specific only to α-form. The data for P(LLA-co-L-2HB) samples in panels (c) and (d) were reproduced from ref 11 with permission from Polymer. Copyright (2015) Elsevier.

Figure 4. Interplanar distance (d) of purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples (a), purified P(LLA-co-D-2HB) and P(LLA-co-L-2HB) samples (b), and melt-quenched-crystallized P(LLA-co-D-2HB) samples and melt-crystallized P(LLA-co-L-2HB) samples (c) as a function of 2HB unit content. The data for P(LLA-co-L-2HB) samples in panels (b) and (c) were reproduced from ref 11 with permission from Polymer. Copyright (2015) Elsevier.

The d values of the purified PLLA sample (α-form) at 2θ = 16.80 and 19.26° were 5.28 and 4.61 Å, respectively, whereas those of the melt-quenched-crystallized PLLA sample [δ- (or α′-)form] at 2θ = 16.54 and 18.86° were 5.36 and 4.71 Å, respectively. The rather dense packing of the former samples compared to the latter sample are ascribed to the difference in

units did not alter the d values. This result as well as narrow crystallizable 2HB unit content range of D-2HB-rich copolymers strongly suggests that only

D-2HB

unit segments

crystallized and LLA units should be excluded from the crystalline regions of D-2HB unit segments. E

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

Figure 5. Crystallinity (Xc) of purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples (a), purified P(LLA-co-D-2HB) and P(LLA-co-L2HB) samples (b), and melt-quenched-crystallized P(LLA-co-D-2HB) samples and melt-crystallized P(LLA-co-L-2HB) samples (c) as a function of 2HB unit content. The data for P(LLA-co-L-2HB) samples in panels (b) and (c) were reproduced from ref 11 with permission from Polymer. Copyright 2015 Elsevier.

Figure 6. DSC thermograms of purified (a), melt-quenched (b), melt-quenched-crystallized (c) P(LLA-co-D-2HB) samples, purified (d), meltquenched (e), and melt-crystallized (f) P(L-2HB), P(LLA-co-L-2HB), and PLLA samples. The data for P(LLA-co-L-2HB) samples in panels (d−f) were reproduced from ref 11 with permission from Polymer. Copyright 2015 Elsevier.

crystalline modification, i.e., α- and δ- (or α′-)forms for the purified and melt-quenched-crystallized PLLA samples, respectively. The d values of the purified HB6 sample (αform) at 2θ = 16.74 and 19.21° were 5.30 and 4.64 Å, respectively, and those of the purified HB11 sample (α-form) at 2θ = 16.78 and 19.22° were 5.28 and 4.62 Å, respectively. These d values were very similar to the purified PLLA samples

(α-form) (5.28 and 4.61 Å), indicating the incorporation of D2HB units with the configuration opposite to LLA units up to 11 mol % in the copolymers did not alter the d values. This result as well as narrow crystallizable 2HB unit content range of LLA-rich copolymers strongly suggests that only LLA unit sequences crystallized and D-2HB units should be excluded from the crystallin regions of LLA unit segments. The d values F

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

crystallization of the major monomer units was stronger for the smaller minor LLA monomer units copolymerized with the larger major D-2HB monomer units than for the larger minor D-2HB monomer units copolymerized with the smaller major LLA monomer units. 3.3. Differential Scanning Calorimetry (DSC). To investigate the thermal properties and cold crystallization during heating of the P(LLA-co-D-2HB) samples, DSC measurements were carried out. Figure 6 shows the DSC thermograms of the purified, melt-quenched, and meltquenched-crystallized P(LLA-co-D-2HB) samples, together with those reported for the purified, melt-quenched, and melt-crystallized P(LLA-co-L-2HB) samples.11 As seen in Figure 6a,c, in addition to a glass transition peak in the range of 20−54 °C, a melting peak was observed at 84−167 °C for the purified P(LLA-co-D-2HB) samples for the 2HB unit content ranges of 0−11 and 95−100 mol % and for the meltquenched-crystallized P(LLA-co-D-2HB) samples for the 2HB unit content ranges of 0−6 and 100 mol %, in agreement with the WAXD results. Again, crystallizable 2HB unit content ranges were narrower for the purified and melt-quenchedcrystallized P(LLA-co-L-2HB) samples than for the purified and melt-crystallized P(LLA-co-L-2HB) samples wherein a melting peak was observed for all the copolymers [Figure 6d,f].11 In the case of the melt-quenched P(LLA-co-D-2HB) samples [Figure 6b], in addition to the glass transition peak in the range of 22−53 °C, cold crystallization and melting peaks (90.6 and 166.5 °C, respectively) were observed for PLLA. This result indicates that only melt-quenched PLLA sample was crystallizable during heating, in agreement with the result reported for the melt-quenched P(LLA-co-L-2HB) samples [Figure 6e].11 The noncrystallizability of the melt-quenched P(D-2HB) or P(L-2HB) samples can be attributed to the small temperature gap between Tm and Tg (approximately 20 and 100 °C, respectively) compared to that between Tm and Tg of PLLA (approximately 55 and 170 °C, respectively), which should reduce the time available for cold crystallization during heating. The noncrystallizability of the melt-quenched copolymers can be ascribed to the same reason for the meltquenched P(D-2HB) or P(L-2HB) samples. The thermal properties obtained from the DSC thermograms in Figure 6 are summarized in Table S2, and the Tg values of the melt-quenched P(LLA-co-D-2HB) samples and the Tm and ΔH(tot) (= ΔHcc + ΔHm) values of the purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples, together with those reported for the P(LLA-co-L-2HB) samples,11 are plotted in Figures 7, 8, and S2, respectively, as a function of 2HB unit content. As seen in Figure 7, the Tg values of the melt-quenched P(LLA-co-D-2HB) samples decreased with an increase in 2HB unit content from 53.3 °C at 2HB unit content = 0 wt % (PLLA) to 22.2 °C at 79.6 wt % (74.5 mol %) and then increased slightly to 25.1 °C at 100 wt % [P(D-2HB)]. In contrast, the Tg values of the meltquenched P(LLA-co-L-2HB) samples decreased monotonically with increasing 2HB unit content from 51.3 °C at 2HB unit content = 0 wt % (PLLA) to 25.3 °C at 100 wt % [P(L2HB)].11 The theoretical Tg values of the melt-quenched P(LLA-co-D-2HB) and P(LLA-co-L-2HB) samples calculated by the following two representative equations37 and shown in dotted and dashed lines in Figure 7:

of the melt-quenched-crystallized HB6 sample (α-form) at 2θ = 16.70 and 18.98° were 5.31 and 4.68 Å, respectively, which are larger than those of the melt-quenched-crystallized PLLA sample [δ- (or α′-)form] (5.36 and 4.71 Å, respectively). This result reflects that the crystalline lattice of the melt-quenchedcrystallized HB6 sample was denser than that of the meltquenched-crystallized PLLA sample. Such decreases of d values of the melt-quenched-crystallized HB6 compared to those of the melt-quenched-crystallized PLLA sample is attributable to the fact that crystalline form difference of δ- (or α′-)form for PLLA and α-form for HB6, as stated above. Figure 4b,c shows the comparison of the d values of the P(LLA-co-D-2HB) and P(LLA-co-L-2HB) copolymers for the purified and melt-(quenched-)crystallized samples. As seen, the d values of both purified and melt-crystallized P(LLA-co-L2HB) samples composed of the monomers with the identical configurations increased linearly with an increase in 2HB unit content, revealing the cocrystallization of the two types of monomer units. In contrast, the d values of both purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples comprising the monomers with the opposite configurations was practically constant for the crystallizable 2HB unit content ranges. This result supports the exclusion of minor monomer units from the crystalline regions of major monomer unit segments. The Xc values of the purified and melt-quenched-crystallized samples were estimated from the WAXD profiles shown in Figure 3. The obtained Xc values are tabulated in Table S1 and plotted in Figure 5 as a function of 2HB unit content. The Xc values of the purified P(D-2HB) sample were 67%, decreased to 29% at LLA unit content of 5 mol % (or at 2HB unit content of 95 mol %), and finally reached nil at LLA unit content of 13% (or at 2HB content of 87 mol %). The Xc value of the melt-quenched-crystallized P(D-2HB) sample was 71% and decreased directly to nil at LLA unit content of 5 mol % (or at 2HB unit content of 95 mol %). On the other hand, the Xc value of the purified PLLA sample was 57%, decreased to 39 and 22% at D-2HB unit content of 6 and 11 mol %, respectively, and finally reached nil at the D-2HB unit content of 16%. The Xc value of the melt-quenched-crystallized PLLA sample was 66%, decreased to 44% at 2HB unit content of 6 mol %, and finally reached nil at D-2HB unit content of 11%. It is interesting to note that the crystallizable 2HB unit content ranges for the purified and melt-quenched-crystallized P(LLAco-D-2HB) samples composed of the monomers with the opposite configurations were much narrower than those for the purified and melt-crystallized P(LLA-co-L-2HB) samples comprising the monomers with the identical configurations [Figure 5b,c]. In other words, the disturbance effect of minor monomer units on the crystallization of the random copolymers was stronger when two types of monomers have the opposite configurations compared to that when two types of monomers have the identical configurations. More interestingly, contrary to the expectations, the crystallizable 2HB unit content ranges of the D-2HB-rich P(LLA-co-D-2HB) samples, 100−95 mol % for the purified samples and 100 mol % for the melt-quenched-crystallized samples, were narrower than those of LLA-rich P(LLA-co-D2HB) samples, 0−11 mol % for the purified samples and 0−6 mol % for the melt-crystallized samples. This result shows that for the random P(LLA-co-D-2HB) copolymers composed of two types of monomer units with the opposite configurations, the disturbance effect of minor monomer units on the G

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

configurations is much higher than that of the melt-quenched P(LLA-co-L-2HB) samples composed of the monomers with the identical configurations. As seen in Figure 8, the Tm values of the purified LLA-rich P(LLA-co-D-2HB) samples dramatically decreased from 166.4 °C at 2HB unit content = 0 mol % (PLLA) to 134.3 and 101.7 °C at 6 and 11 mol %, respectively, and finally disappeared at 2HB unit content over 11 mol %, whereas the Tm values of the melt-quenched-crystallized LLA-rich P(LLA-co-D-2HB) samples decreased more dramatically from 166.5 °C at 2HB unit content = 0 mol % (PLLA) to 133.9 °C at 6 mol % and disappeared at 2HB unit content over 6 mol %. The Tm values of the purified D -2HB-rich P(LLA-co- D -2HB) samples decreased from 98.9 °C at 2HB unit content = 100 mol % [P(D-2HB)] to 83.5 °C at 95.2 mol %, and finally disappeared at 2HB unit content below 95.2 mol %, and the Tm value of the melt-quenched-crystallized D-2HB-rich P(LLA-co-D-2HB) sample was observed only at 2HB unit content = 100 mol % [P(D2HB)] (102.3 °C). These trends for the purified and meltquenched-crystallized P(LLA-co-D-2HB) samples are different from those for the purified and melt-crystallized P(LLA-co-L2HB) samples, wherein although Tm values decreased with deviating from 2HB unit content = 0 or 100 mol %, the Tm values of P(LLA-co-L-2HB) samples at 2HB unit content = 26.6, 44.0, and 73.7 mol % (103.9, 94.8, and 93.3 °C, respectively) were similar to the Tm values of P(L-2HB) samples (102.6 °C). Finally, the trend observed for ΔH(tot) values of the purified and melt-quenched-crystallized P(LLAco-D-2HB) samples, which can be an indicator of crystallinity, was consistent with that for Xc (Figure S3).

Figure 7. Glass transition temperature (Tg) of melt-quenched P(LLAco-D-2HB) and P(LLA-co-L-2HB) samples as a function of 2HB unit content. The data for melt-quenched P(LLA-co-L-2HB) samples were reproduced with permission from is reproduced from ref 11 with permission from Polymer. Copyright 2015 Elsevier. The dashed and dotted lines show the theoretical values calculated by eqs 1 and 2, respectively.

Tg (copolymer) = [1 − 2HB unit content (wt%)/100]Tg (PLLA) + [2HB unit content (wt%)/100] Tg[P(L‐2HB) or P(D‐2HB)]

(1)

1/Tg (copolymer) = [1 − 2HB unit content (wt%)/100] /Tg (PLLA) + [2HB unit content (wt%)/100] /Tg[P(L − 2HB) or P(D − 2HB)]

4. CONCLUSIONS In the present study, as model polymers composed of optically active monomer units with the opposite configurations, P(LLA-co-D-2HB) copolymers composed of L-configured LLA units and D-configured D-2HB units with the opposite configurations and the 2HB unit contents from 0 to 100 mol % were synthesized by polycondensation, and their crystallization behavior was compared with that reported for the random copolymers composed of optically active L-lactic acid and L-2hydroxybutanoic acid (L-2HB) [P(LLA-co-L-2HB)s] with the identical configurations. WAXD and DSC results indicated that the P(LLA-co-D-2HB) copolymers were crystallizable at 2HB unit contents only around 0 and 100 mol % (i.e., 0−11 and

(2)

where Tg(PLLA) and Tg[P(L-2HB) or P(D-2HB)] are the Tg values of PLLA and P(L-2HB) or P(D-2HB), respectively. The experimental Tg values of the melt-quenched P(LLA-co-D2HB) and P(LLA-co-L-2HB) samples largely deviated from the theoretical values calculated by the two equations. The experimental Tg values were much lower for the meltquenched P(LLA-co-D-2HB) samples than for the meltquenched P(LLA-co-L-2HB) samples. This result indicates that the segmental mobility of the melt-quenched P(LLA-co-D2HB) samples composed of the monomers with the opposite

Figure 8. Melting temperature (Tm) of purified and melt-quenched-crystallized P(LLA-co-D-2HB) samples (a), purified P(LLA-co-D-2HB) and P(LLA-co-L-2HB) samples (b), and melt-quenched-crystallized P(LLA-co-D-2HB) samples and melt-crystallized P(LLA-co-L-2HB) samples (c) as a function of 2HB unit content. The data for P(LLA-co-L-2HB) samples in panels (b) and (c) were reproduced from ref 11 with permission from Polymer. Copyright 2015 Elsevier. H

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

(6) Garlotta, D. A Literature Review of Poly(Lactic Acid). J. Polym. Environ. 2001, 9, 63−84. (7) Södergård, A.; Stolt, M. Properties of Lactic Acid Based Polymers and Their Correlation with Composition. Prog. Polym. Sci. 2002, 27, 1123−1163. (8) Albertsson, A.-C., Ed. Degradable Aliphatic Polyesters; Springer, Berlin, Germany, 2002; Advances in Polymer Science, Vol. 157. (9) Doi, Y., Steinbüchel, A., Eds. Polyesters I, II, III (Biopolymers; Wiley-VCH: Weinheim, Germany, 2002; Vol. 3a, 3b, 4. (10) Auras, R., Lim, L.-T., Selke, S. E. M., Tsuji, H., Eds. Poly(lactic acid): Synthesis, Structures, Properties, Processing, and Applications (Wiley Series on Polymer Engineering and Technology); John Wiley & Sons, Inc.: NJ, 2010. (11) Tsuji, H.; Sobue, T. Cocrystallization of Monomer Units in Lactic Acid-Based Biodegradable Copolymers, Poly(L-lactic acid-co-L2-hydroxybutanoic acid)s. Polymer 2015, 72, 202−211. (12) Tsuji, H.; Sobue, T. \blendnay quatenary Stereocomplexation of Quaternary or Ternary Monomer Unitsand Dual Stereocomplexation in Enantiomeric Binary and Quaternary Polymer Blends of Poly(2-hydroxybutanoic acid)s, Poly(2-hydroxybutanoic acid-co-lactic acid)s, and Poly(lactic acid)s. RSC Adv. 2015, 5, 83331−83342. (13) Kabe, T.; Matsumoto, K.; Terai, S.; Hikima, T.; Takata, M.; Miyake, M.; Taguchi, S.; Iwata, T. Co-crystallization Phenomena in Biosynthesized Isotactic Poly[(R)-lactate-co-(R)-2-hydroxybutyrate]s with Various Lactate Unit Ratios. Polym. Degrad. Stab. 2016, 132, 137−144. (14) Gilding, K.; Reed, A. M. Biodegradable Polymers for Use in Surgery-Polyglycolic/Poly(lactic acid) Homo- and Copolymers: 1. Polymer 1979, 20, 1459−1464. (15) Chatani, Y.; Suehiro, K.; Okita, Y.; Tadokoro, H.; Chujo, K. Structual Studies of Polyersters. I. Crystal Structure of Polyglycolide. Makromol. Chem. 1968, 113, 215−229. (16) Marubayashi, H.; Asai, S.; Hikima, T.; Takata, M.; Iwata, T. Biobased Copolymers Composed of L-Lactic Acid and Side-ChainSubstituted Lactic Acids: Synthesis, Properties, and Solid-State Structure. Macromol. Chem. Phys. 2013, 214, 2546−2561. (17) Wang, Z.-Y.; Zhao, Y.-M.; Wang, F.; Wang, J. Syntheses of Poly(lactic acid-co-glycolic acid) Serial Biodegradable Polymer Materials via Direct Melt Polycondensation and Their Characterization. J. Appl. Polym. Sci. 2006, 99, 244−252. (18) Tsuji, H.; Kikkawa, K.; Arakawa, Y. Cocrystallization of Monomer Units of Biobased and Biodegradable Poly(L-lactic acid-coglycolic acid) Random Copolymers. Polym. J. 2018, 50, DOI: 10.1038/s41428-018-0093-z. (19) Tsuji, H.; Osanai, K.; Arakawa, Y. Stereocomplex Crystallization between L- and D-Configured Staggered Asymmetric Random Copolymers Based on 2-Hydroxyalkanoic Acids. Cryst. Growth Des. 2018, DOI: 10.1021/acs.cgd.8b00863. (20) Tsuji, H.; Matsuoka, H.; Itsuno, S. Synthesis, Physical Properties, and Crystallization of Optically Active Poly(L-phenyllactic acid) and Poly(L-phenyllactic acid-co-L-lactic acid). J. Appl. Polym. Sci. 2008, 110, 3954−3962. (21) Tsuji, H.; Sato, S.; Masaki, N.; Arakawa, Y.; Kuzuya, A.; Ohya, Y. Synthesis, Stereocomplex Crystallization and Homo-Crystallization of Enantiomeric Poly(lactic acid-co-alanine)s with Ester and Amide Linkages. Polym. Chem. 2018, 9, 565−575. (22) Tsuji, H.; Ikada, Y. Stereocomplex Formation between Enantiomeric Poly(lactic acid)s. 6. Binary Blends from Copolymers. Macromolecules 1992, 25, 5719−5723. (23) Tsuji, H.; Ikada, Y. Crystallization from the Melt of Poly(lactide)s with Different Optical Purities and Their Blends. Macromol. Chem. Phys. 1996, 197, 3483−3499. (24) Ovitt, T. M.; Coates, G. W. Selective Ring-Opening Polymerization of meso-Lactide: Synethsis of Syndiotactic Poly(Lactic acid). J. Am. Chem. Soc. 1999, 121, 4072−4073. (25) Tsuji, H.; Arakawa, Y. Synthesis, Properties, and Crystallization of the Alternating Stereocopolymer Poly(L-lactic acid-alt-D-lactic acid) [Syndiotactic Poly(lactic acid)] and Its Blend with Isotactic Poly(lactic acid). Polym. Chem. 2018, 9, 2446−2457.

95−100 mol %), whereas P(LLA-co-L-2HB) copolymers were reported to be crystallizable at all 2HB contents from 0 to 100 mol %. These results that the disturbance effect of minor monomer units with the configuration opposite to that of the major monomer units on the crystallization of the random copolymers is much stronger than that of the minor monomer units with the configuration identical to that of the major monomer units. There is another difference in the crystallization behavior between the P(LLA-co-D-2HB) copolymers and the P(LLA-co-L-2HB) copolymers. WAXD results strongly suggested that the minor monomer units were excluded from the crystalline regions of the major monomer units when two types of monomers have the opposite configurations, although the minor monomer units are reported to be incorporated in the crystalline regions of the major monomer units when two types of monomers have the identical configurations. DSC results exhibited that the segmental mobility of the meltquenched P(LLA-co-D-2HB) samples composed of the monomers with the opposite configurations is much higher than that of the melt-quenched P(LLA-co-L-2HB) samples composed of monomers with identical configurations.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.cgd.8b01023. (1) 13C NMR spectra of carbonyl carbon for P(L-2HB), P(LLA-co-L-2HB) with 2HB unit content of 44 mol % (HB44), and PLLA; (2) magnified WAXD profiles of purified and melt-quenched-crystallized PLLA, HB6, and HB11 samples; (3) interplanar distance (d) and crystallinity (Xc) values of P(D-2HB), P(LLA-co-D2HB), and PLLA samples; (4) thermal properties of purified, melt-quenched, and melt-quenched-crystallized samples; (5) ΔH(tot) (=ΔHcc + ΔHm) of purified and melt-quenched-crystallized samples (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Hideto Tsuji: 0000-0001-9986-5933 Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS This research was partly supported by JSPS KAKENHI Grant No. 16K05912. REFERENCES

(1) Vert, M., Feijen, J., Albertsson, A.-C., Scott, G., Chiellini, E., Eds. Biodegradable Polymers and Plastics; Royal Society of Chemistry: Cambridge, 1992. (2) Mobley, D. P., Ed. Plastics from Microbes; Hanser Publishers: New York, 1994. (3) Vert, M.; Schwarch, G.; Coudane, J. Present and Future of PLA Polymers. J. Macromol. Sci., Part A: Pure Appl.Chem. 1995, 32, 787− 796. (4) Domb, A. J.; Kost, J.; Wieseman, D. M., Eds. Handbook of Biodegradable Polymers; Harwood Academic Publishers: Amsterdam, The Netherlands, 1997; Drug Targeting and Delivery, Vol. 7. (5) Kaplan, D. L., Ed. Biopolymers from Renewable Resources; Springer: Berlin, Germany, 1998. I

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

(26) Tabata, Y.; Abe, H. Synthesis and Properties of Alternating Copolymers of 3-Hydroxybutyrate and Lactate Units with Different Stereocompositions. Macromolecules 2014, 47, 7354−7361. (27) Tsuji, H.; Hayakawa, T. Heterostereocomplex Formation between Substituted Poly(lactic acid)s with Linear and Branched Side Chains, Poly(L-2-hydroxybutanoic acid) and Poly(D-2-hydroxy-3methylbutanoic acid). Polymer 2014, 55, 721−726. (28) Tsuji, H.; Ikada, Y. Properties and Morphologies of Poly(Llactide): 1. Annealing Condition Effects on Properties and Morphologies of Poly(L-lactide). Polymer 1995, 36, 2709−2716. (29) Pan, P.; Zhu, B.; Kai, W.; Dong, T.; Inoue, Y. Effect of Crystallization Temperature on Crystal Modifications and Crystallization Kinetics of Poly(L-lactide). J. Appl. Polym. Sci. 2008, 107, 54− 62. (30) Tsuji, H.; Tashiro, K.; Bouapao, L.; Hanesaka, M. Separate Crystallization and Cocrystallization of Poly(L-lactide) in the Presence of L-Lactide-Based Copolymers with Low Crystallizability, Poly(Llactide-co-glycolide) and Poly(L-lactide-co-D-lactide). Macromol. Chem. Phys. 2012, 213, 2099−2112. (31) Zhang, J.; Tashiro, K.; Tsuji, H.; Domb, A. J. Investigation of Phase Transitional Behavior of Poly(L-lactide)/Poly(D-lactide) Blend Used to Prepare the Highly-Oriented Stereocomplex. Macromolecules 2007, 40, 1049−54. (32) Pan, P.; Kai, W.; Zhu, B.; Dong, T.; Inoue, Y. Polymorphous Crystallization and Multiple Melting Behavior of Poly(L-lactide): Molecular Weight Dependence. Macromolecules 2007, 40, 6898− 6905. (33) Pan, P.; Liang, Z.; Zhu, B.; Dong, T.; Inoue, Y. Blending Effects on Polymorphic Crystallization of Poly(L-lactide). Macromolecules 2009, 42, 3374−3380. (34) Wasanasuk, K.; Tashiro, K. Crystal Structure and Disorder in Poly(l-lactic acid) δform (α′ form) and the Phase Transition Mechanism to the Ordered α form. Polymer 2011, 52, 6097−6109. (35) Tsuji, H.; Okumura, A. Stereocomplex Formation between Enantiomeric Substituted Poly(lactide)s: Blends of Poly[(S)-2hydroxybutyrate] and Poly[(R)-2-hydroxybutyrate]. Macromolecules 2009, 42, 7263−6. (36) Tsuji, H.; Yamamoto, S.; Okumura, A.; Sugiura, Y. Heterostereocomplexation between Biodegradable and Optically Active Polyesters as a Versatile Preparation Method for Biodegradable Materials. Biomacromolecules 2010, 11, 252−258. (37) See for example, Young, R. J.; Lovell, P. A. Introduction to Polymers, 3rd ed.; CRC Press: Boca Rato, FL, 2011; Chapter 16, pp 383−397.

J

DOI: 10.1021/acs.cgd.8b01023 Cryst. Growth Des. XXXX, XXX, XXX−XXX