Enhancing the Crystallization Performance of Poly(L-lactide) by Intramolecular Hybridizing with Tunable Self-assembly-type Oxalamide Segments

In this work, hydroxyl-terminated oxalamide compounds N1,N2-bis(2-hydroxyethyl)oxalamide (OXA1) and N1, N1′-(ethane-1,2-diyl)bis(N2-(2-hydroxyethyl)oxalamide (OXA2) were synthesized to initiate the ring-opening polymerization of L-lactide for preparation of oxalamide-hybridized poly(L-lactide) (PLAOXA), i.e., PLAOXA1 and PLAOXA2. The crystallization properties of PLA were improved by the self-assembly of the oxalamide segments in PLAOXA which served as the initial heterogeneous nuclei. The crystal growth kinetics was studied by Hoffman-Lauritzen theory and it revealed that the nucleation energy barrier of PLAOXA1 and PLAOXA2 was lower than that of PLA. Consequently, PLAOXA could crystallize much faster than PLA, accompanied with a decrease in spherulite size and half-life crystallization time by 74.8% and 86.5% (T = 125 °C), respectively. In addition, the final crystallinity of PLAOXA1 and PLAOXA2 was 6 and 8 times higher, respectively, in comparison with that of neat PLA under a controlled cooling rate of 10 °C/min. The results demonstrate that the hybridization of oxalamide segments in PLA backbone will serve as the self-heteronucleation for promoting the crystallization rate. The higher the content of oxalamide segments (PLAOXA2 compared with PLAOXA1) is, the stronger the promotion effect will be. Therefore, this study may provide a universal approach by hybridizing macromolecular structure to facilitate the crystallization of semi-crystalline polymer materials.


INTRODUCTION
With the awareness of environmental protection, an irresistible trend of "plastic limit" and "plastic ban" has gradually formed in recent years. United Nations Environment Programme and World Resources Institute have claimed that at least 127 countries have made regulations to against plastic bags. [1] Apparently, biodegradable polymer materials have been attracting more and more attention. Among them, poly(lactide) (PLA) has been developed rapidly attributed to its outstanding biocompatibility, processability, high tensile strength and elastic modulus. PLA has already been applied in packaging, textiles, and biomedical areas. [2,3] However, the low heat deflection temperature (HDT), melt strength, and crystallinity limit its utilization as a high performance bioplastic. [4−6] Therefore, improving the crystallization performance becomes a crucial point during the processing of PLA.
Beside the incorporation of a nucleating agent, many studies were trying to improve the crystallization performance of PLA by tailoring its molecular structures using the active end groups (-OH and -COOH). For example, Pan et al. [24] prepared 2-ureido-4[1H]-pyrimidione (UPy)-bonded supramolecular PLLA (SM-PLLA) by using UPy-terminated low-molecular-weight (LMW) PLLA, and its crystallization kinetics and polymorphic crystalline structure were compared with the conventional PLLA. Although the crystallization rate and crystallinity of the SM-PLLA were depressed, it provided an alternative for the investigation of PLA crystals. Kodal et al. [25] investigated the effects of epoxy functionalized poly(hedral oligomeric silsesquioxane) (G-POSS) nanoparticles, which was then grafted onto the ends of PLA chain, on the crystallization performance of PLA. The results indicated that the epoxy group of G-POSS can accelerate the crystallization rate during cooling, which is supposed to be responsible for the inter-/intramolecular physical (H-bonding) or chemical (covalent) interactions among the end groups of PLA. Meanwhile, some researchers have also prepared the PLA hybrids, such as PEGylated PLA-phospholipon [26] and silica groups [27] at the end of PLA chain. The results showed that both the crystallinity and the toughness of PLA were improved. Therefore, the intermolecular interaction is condu-cive to the crystallization of PLA, and the crystallization performance of PLA was improved by the molecular design and synthesis.
In consideration of the advantages of amide nucleating agent mentioned above, we designed the oxalamide segments (OXA) as self-heteronucleation site in the PLA backbone to provide a new approach to enhance the crystallization of PLA. The OXA-functionalized PLA was then designed, synthesized, and characterized, and the effect of OXA segments on the crystallization kinetics of PLA was investigated as well.

Sample Preparation Preparation of OXA1 initiator
The N 1 ,N 2 -bis(2-hydroxyethyl) oxalamide, shorted as OXA1, was synthesized according to the method reported previously. [28] Briefly, diethyl oxalate (6.8 mL, 0.05 mol) was dissolved in 70 mL of ethanol solution in a 250 mL round-bottom flask. Then ethanolamine (15 mL, 0.25 mol, 5-fold excess) was added dropwise in this solution and the mixture was mechanically stirred at 400 r/min for 24 h to get the precipitates. The precipitates were then filtered using a Büchner funnel, and washed with ethanol and dried in the vacuum oven at 60 °C to yield a white-powder (5.56 g, 53.6%). The reaction is shown in Fig. 1 Sci. 2021, 39, 122-132 Preparation of PLA OXA1 OXA1 and the purified L-lactide were dried in a vacuum oven for 12 h at 60 °C before use. The preparation of PLA OXA1 was carried out as following: the purified L-lactide (10 g, 0.07 mol), OXA1 (0.5 g, 0.0028 mol), and Sn(Oct) 2 (0.05 g, 0.5%) were mixed at 135 °C for 24 h. The product was named as PLA OXA1 (8.06 g, 76.8%). The reaction is schematically shown in Fig. 1(b).

Synthesis of PLA OXA2
OXA2 and the purified L-lactide were dried in a vacuum oven for 12 h at 60 °C before use. The preparation of PLA OXA2 was carried out as following: the purified L-lactide (10 g, 0.07 mol) in toluene, OXA2 (0.5 g, 0.0017 mol), and Sn(Oct) 2 (0.05 g, 0.5 wt%) were mixed and at 135 °C for 24 h. The product was named as PLA OXA2 (7.92 g, 75.4%). The reaction is schematically shown in Fig. 1(e). For comparison, PLA (6.88 g, 65.5%) was also synthesized via ring-opening polymerization initiated by the trace amount of water.

Fourier transformed infrared (FTIR)
The infrared absorption spectra of the synthesized OXA1, DEO, OXA2, PLA, PLA OXA1 , and PLA OXA2 were analyzed using a total reflection Fourier transform infrared spectrometer (Nicolet 6700, USA Thermo Fisher Scientific). The final spectrum of each sample was obtained at a resolution of 4 cm −1 in the wavenumber range of 500−4000 cm −1 with an average of 32 scans.

Gel permeation chromatography (GPC)
The molecular weights and molecular weight distributions of the synthesized PLA, PLA OXA1 , and PLA OXA2 were measured by gel permeation chromatography (Waterside, USA) in tetrahydrofuran (THF) by using polystyrene as a standard. The THF solutions of each sample were diluted to a concentration of 1.0 mg/mL for all GPC experiments. Then the diluted solutions were filtered through a 0.22 μm needle-type organic filter membrane, and 20 μL of each filtered solution was injected into the system through a sampler.

Differential scanning calorimetry (DSC)
The crystallization behavior was studied by differential scanning calorimetry (DSC 8000, Perkin Elmer). For non-isothermal crystallization experiments, the samples were heated to 180 °C at 30 °C/min and held for 3 min to remove thermal history. Subsequently, the samples were cooled to 0 °C at a cooling rate of 10 °C/min and then heated up to 180 °C at 10 °C/min. For isothermal crystallization experiments, after melting at 180 °C for 3 min, the samples were cooled to 125 °C at 100 °C/min and then held at this temperature for crystallization. The process diagrams of non-isothermal crystallization and isothermal crystallization are shown in Fig. S1 (in the electronic supplementary information, ESI). All tests were carried out in a nitrogen atmosphere.

Wide angle X-ray diffractometry (WAXD)
The samples were evaluated by an X-ray diffractometer (Bruker AXS D8, Germany) equipped with a Ni-filtered Cu Kα X-ray source at a wavelength of 0.154 nm. The measurements were conducted at 40 kV and 40 mA with scan angles (2θ) from 3°t o 35° at a scan rate of 3 (°)/min.

Polarized optical microscopy (POM)
The evolutions in crystal morphology during non-isothermal and isothermal crystallization were monitored with a POM (Axio Imager A2POL polarizing microscope, Zeiss, Germany) in combination with a Linkam THMS600 hot stage. The samples of PLA, PLA OXA1 , and PLA OXA2 were sandwiched between two clean glass slides, and then melted at 180 °C for 3 min, followed by cooling down to 125 °C at 40 °C/min for isothermal crystallization. The detailed conditions of the non-isothermal crystallization test are the same as that of DSC. The morphological changes during the heating and the cooling cycle were monitored by a digital camera to record the process of crystal growth and morphology.

Rheological behavior
Rheological experiments were implemented by a DHR-2 rheometer (TA Instruments, USA) in a plate-plate configuration to study the effects of self-assembly of OXA segments on the crystallization of PLA, PLA OXA1 , and PLA OXA2 . Then the sheets were cut into circular shape specimens for the rheological (25 mm of diameter, 1 mm of thickness) measurements. The samples were annealed at 180 °C for 3 min and subjected to a dynamic temperature sweep with a ratio of −5 °C/min to the desired crystallization temperature. The strain and frequency were set as 1% and 1 Hz, respectively. show that the intensity of oxalamide segments of PLA OXA2 is approximately twice higher than that of PLA OXA1 . All these results clearly indicate that OXA2 and PLA OXA2 have been successfully synthesized and the structure is clear. (The 1 H-NMR spectra of DEO and PLA are shown in Fig. S2 in ESI).

RESULTS AND DISCUSSION
The FTIR spectra of the synthesized PLA, OXA1, and PLA OXA1 are shown in Fig. 3(a). The characteristic bands of OXA1 are found at 3300 cm −1 (ν N-H ), 1650 cm −1 (amide I, ν C＝O ), 1550− 1450 cm −1 (amide II, ν C-N +δ N-H ), and 1320−1250 cm −1 (amide III, ν C-N +δ N-H ). In the PLA OXA1 spectrum, the band at 1750 cm −1 is attributed to the C＝O vibration of PLA, while the band at 1650 cm −1 (associated with the C＝O stretching vibration on the amide I band of OXA1) shifts to 1678 cm −1 . This can be explained as that the hydrogen-bonding interaction formed between the OXA1 segments in the PLA OXA1 backbone was weakened when compared with OXA1 compound. These results indicate that OXA1 and PLA OXA1 are successfully prepared. Fig. 3 A similar phenomenon was also observed in poly(ether amide)s system. [29] Thus, FTIR spectra evidenced that a more extensive hydrogen bonding could be formed in the order of hard segments consisting of multiple oxalamide groups, in respect to that comprising of single oxalamide unit. The molecular weights (M n and M w ) and polydispersity indexes (PDI) of PLA, PLA OXA1 , and PLA OXA2 were characterized by gel permeation chromatography (polystyrene standard), and the results are shown in Table 1.

Non-isothermal Crystallization and Crystal Morphology Analysis
Figs. 4(a) and 4(b) show the cooling and second heating scan curves of PLA and PLA OXA detected by DSC. It can be seen that the crystallization of PLA is slow and no discernible crystallization peak was visible in the cooling process. For PLA OXA1 and PLA OXA2 , the crystallization peaks appeared at around 105 and 108 °C, respectively. Moreover, during the subsequent heating scans, the cold crystallization enthalpy of PLA OXA was significantly decreased. Compared with PLA, PLA OXA1 had two amide groups next to each other in reverse, which allowed the formation of two hydrogen bonds per oxalamide motif, resulting in an increased tendency to crystallize into sheet-like structures. [30] With a higher content of amide groups in molecule, the cold crystallization enthalpy of PLA OXA2 was further decreased. The crystallinity (X c ) of PLA, PLA OXA1 , and PLA OXA2 can be calculated by Eq. (1): where ΔH m and ΔH cc are melt and cold crystallization enthalpies of PLA, respectively, ω is the weight proportion of PLA in PLA OXA , while =93.6 J/g is the melting enthalpy of PLA with a crystallinity of 100%. [28,31] X c of PLA OXA1 and PLA OXA2 was 23.6% and 57.6%, respectively, while it is only 11.8% for PLA ( Table 2). The amide groups in polymers may form original nucleus due to the  N-H···O＝C hydrogen bonding, which makes the PLA chains easier to pile up and crystallize. Besides, a higher content of oxalamide segments has stronger promotion effect on the PLA crystallization rate and crystallinity. The formation of PLA, PLA OXA1 , and PLA OXA2 crystallites was also evidenced by WAXD analysis and the results are presented in Fig. 4(c). The diffraction peak intensity of PLA OXA is significantly larger than that of PLA, indicating a higher crystallinity, which is consistent with the DSC results. 2θ=13.7°, 16.8° and 19.2° are assigned to the (010), (200)/(110), and (203) planes of PLA α crystal, [32] respectively, which indicated that the amide groups of PLA OXA did not change its crystal form. [33] The crystal morphology evolution of PLA, PLA OXA1 , and PLA OXA2 in non-isothermal crystallization is observed by POM and the results are shown in Fig. 5. Only sparse spherulites could be observed for PLA when it was cooled from 110 °C to 30 °C. In contrast, in the cases of PLA OXA1 and PLA OXA2 , lots of small spherulites appeared at 110 °C, and more spherulites were visible when the temperature decreased to 30 °C. The POM results indicated that the density of PLA OXA2 spherulites was higher than that of PLA OXA1 , whereas the size was not obviously varied. According to the Gutzow and Dobreva models, [34] PLA OXA had higher nucleation efficiency than that of PLA ( Fig. S3 and Table S1 in ESI).

Isothermal Crystallization and Crystal Morphology Analysis
Figs. 6(a) and 6(b) exhibit the DSC isothermal heat flow and relative crystallinity curves of PLA, PLA OXA1 , and PLA OXA2 crystallized at 125 °C as a function of time. The crystallization of PLA was not completed until 35 min, while PLA OXA1 and PLA OXA2 showed obvious isothermal crystallization peaks and could crystallize completely within 8 and 4 min, respectively. These results prove again that the amide groups in polymers could accelerate the crystallization of PLA segments.
Avrami equation [35] (Eq. 2) was used to describe the isothermal crystallization kinetics of PLA and PLA OXA1 samples at 125 °C : where X t is the relative crystallinity, n is the Avrami exponent, k is the crystallization rate constant, and t is the crystallization time.
The linear fitting of log[−ln(1 − X t )] versus log(t) is shown in Fig. 6(c). A linear portion of relative crystallinity was used to calculate n and k, as shown in Table 3. For the ideal isothermal crystallization process, n should be an integer, which depends on the nucleation mechanism and the growth mode. The n value of the samples in this study is non-integer, between 2.7−3.5, suggesting that the polymer crystals may be a combination of flaky crystal and three-dimensional spherulites. [36] The half-life crystallization time (t 1/2 ) of PLA, PLA OXA1 , and PLA OXA2 at 125 °C can be calculated by Eq. (3). Table 2 Non-isothermal crystallization parameters of PLA, PLA OXA1 , and PLA OXA2 .
Note: T c is the crystallization temperature, ΔH c is the temperature drop crystallization enthalpy, T cc is the cold crystallization temperature, ΔH cc is the cold crystallization enthalpy, T m is the melting point, ΔH m is the melting enthalpy. X c is calculated from the DSC data by Eq. (1), while X c ' is calculated from and X c * is calculated from the WAXD data.  Fig. 7 shows the POM images of PLA, PLA OXA1 , and PLA OXA2 isothermally crystallized at T c =125 °C, where the spherulites are clearly visible. Compared to PLA and PLA OXA1 , a large number of spherulites in PLA OXA2 started to form after 30 s and the crystallization process was finished in 5 min. The POM images offer a visual insight into the nucleation efficiency of different OXA segments, which are well in agreement with above DSC discussions (Fig. 6). The phenomena confirm that the introduction of amide groups in PLA chain can increase the crystallization rate and crystallinity. Moreover, the spherulite size decreased significantly at a higher amide group content. In applications, a short crystallization time is beneficial to shortening the molding time. [37] Meanwhile, the higher crystallinity of PLA products will also contribute to the satisfactory mechanical properties such as yield stress, strength, modulus and hardness.
In order to further investigate the crystallization kinetics of PLA OXA , the well-known Hoffman-Lauritzen crystallization mechanism is applied. [38] According to this mechanism, three regimes of polymer crystallization, i.e. regimes I, II, and III, are distinguished, while the crystal growth rate (G) could determine regime assignment. Fig. 8(a) shows the temperaturedependence behavior of G values for PLA, PLA OXA1 , and PLA OXA2 , which was obtained by POM observation at different temperatures. G of PLA OXA2 increased gradually with reducing the temperature from 130 °C to 110 °C, and exhibited the maximum value (0.23 μm/s) at 115 °C. The same trend and maximum value (0.21 μm/s, 115 °C) were observed for PLA OXA1 as well. PLA showed lower G than that of PLA OXA at the same temperature. The results demonstrate that the introduction of amide groups can facilitate the crystal growth of PLA. A similar phenomenon was also observed in the system of PLA/N 1 ,N 1 ′-(ethane-1,2-diyl)bis(N 2 -phenyloxalam-ide). [39] According to Hoffman-Lauritzen theory, the crystallization kinetics of PLA, PLA OXA1 , and PLA OXA2 can be expressed by Eq. (4): where G is the crystal growth rate (shown in Fig. 8a), T c is the isothermal crystallization temperature (125 °C), R is the gas constant, G 0 is the pre-exponential factor, T ∞ = T g -30 K. U * represents the activation energy required for crystallization, , is the equilibrium melting point of the samples, , and K g is the nucleation constant, as shown in the following Eq. (5): Δh f k (5) where σ and σ e are the lateral and end-surface free energies, respectively, b 0 is a monatomic (or monomolecular) layer of fixed thickness, and k is the Boltzmann constant. The values of m, which is dependent on the regime of crystallization, are determined as 4, 2, and 4 for regimes I, II, and III, respectively. Eq. (4) is mathematically deformed and it can be expressed as: The crystal growth kinetics of PLA, PLA OXA1 , and PLA OXA2 are shown in Fig. 8(b). It was found that PLA, PLA OXA1 , and PLA OXA2 had two linear regions, which represent the crystallization mechanism II at higher temperatures and the crystallization mechanism III at lower temperatures, respectively. K g III of PLA, PLA OXA1 and PLA OXA2 was 8.1×10 8 K 2 , 6.0×10 8 K 2 and 3.1×10 8 K 2 , respectively, while K g II of PLA, PLA OXA1 and PLA OXA2 was 3.2×10 8  ively. The smaller the K g III or K g II value is, the smaller the nucleation energy barrier of PLA OXA1 and PLA OXA2 is needed to surmount. [40]

Proposed Nucleation and Crystallization Mechanism of PLA OXA
There have been numerous studies in the nucleation mechanism of organic and inorganic agents in promoting PLA crystallization, [41,42] but self-assembly mechanism of the intramolecular nucleating agents is rarely investigated. Fig. 9 shows the variation of storage modulus with temperature for the PLA, PLA OXA1 , and PLA OXA2 melts during cooling. When the temperature of PLA decreased from 180 °C to 100 °C, the storage modulus rose sharply around 115 °C. Only one transition point of storage modulus appeared for pure PLA, whereas two transition points for PLA OXA1 and PLA OXA2 samples could be observed at 130/119 and 145/123 °C, respectively. The former one at the higher temperature was mainly attributed to the self-assembly of OXA segments via the hydrogen bonds, which was confirmed by the 1 H-NMR spectra (Figs. 2b and 2d) and the FTIR spectrum (Fig.  3c), causing the melt modulus to rise rapidly in the cooling process. The latter one at the lower temperature was mainly associated with the rapid crystallization of the PLA chains. Recent studies show that polymer crystallization accelerated by nucleating agents involved several mechanisms including the epitaxial growth on nucleator surface, [43] chemical reaction, [44] and hydrogen bonding interactions [45] between nucleator and polymer. Xing et al. proposed that the hydrogen bonding between -NH groups of hydrazidetype nucleator and -C＝O groups of PLA can promote nucleation and folding crystallization of the PLA chains. In this work, the amide groups are embedded in the PLA chain to form the hydrogen bonds, thereby promoting crystallization. On the basis of the aforementioned results, a schematic illustration is proposed for the mechanism discussion, i.e., the hydrogen bonds between the OXA segments inducing the nuc-leation and crystallization of PLA OXA , as shown in Fig. 10. In the melt state, the PLA chains are in random coil state and OXA segments are in the middle of the PLA backbone, which is illustrated in Fig. 10(a). In the cooling process, hydrogen bonds are formed between amide groups to accelerate the generation and growth of original nuclei, and PLA chains close to the amide groups could be quickly accumulated and crystallized forming microcrystalline. The presence of original nuclei will reduce the activation energy and provide a large number of nucleation sites for crystallization of PLA OXA chains, as illustrated in Figs. 10(b) and 10(c). The original nuclei have high nucleation activity, which can improve the crystallization rate and crystallinity of PLA OXA .

CONCLUSIONS
In this study, novel hydroxyl-terminated oxalamide nucleating agents were synthesized and used to initiate the ring-opening polymerization of L-lactide for preparing PLA OXA1 and PLA OXA2 . Non-isothermal crystallization behavior showed that PLA OXA crystallized faster than neat PLA, and the crystallinity increased from 11.8% (PLA) up to 23.6% (PLA OXA1 ) and 57.6% (PLA OXA2 ), respectively. The isothermal crystallization showed that the half-life crystallization time at 125 °C was shortened from 16.3 min (PLA) to 4.1 (PLA OXA1 ) and 2.2 min (PLA OXA2 ). In the meanwhile, the crystal growth kinetics of PLA OXA was studied based on Hoffman-Lauritzen theory and it revealed that both K g III and K g II values of PLA OXA were lower than those of PLA, indicating that the nucleation energy barrier for PLA OXA is lower. Therefore, the hybridization of oxalamide segments in backbone of PLA facilitated the self-assembling between amide groups in different PLA chains, and then served as selfheteronucleation for accelerating the crystallization rate and increasing the crystallinity of PLA. In addition, PLA OXA2 had PLA PLA OXA1 PLA OXA2

Self-assembly of H-bond
Crys of PLA greater enhancement effects on the crystallization kinetics than PLA OXA1 , which was ascribed to the higher content of oxalamide segments. Thus, this study may provide a universal approach of hybridizing molecular chain to enhance the crystallization performance for versatile polymer materials.

Electronic Supplementary Information
Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://dx.doi.org/ 10.1007/s10118-020-2461-3.