Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers

D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as “a configurational or helical molecular glue” for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

As stated above, the stereocomplexation was observed for the blends up to quaternary polymers or monomer units. Although the reported polymer blends which form SC crystallites contain the polymers with the identical or two different chemical structures, a stereocomplexationable polymer blend which comprises the polymers with three or more different chemical structures has not reported so far. This article reports for the first time an example of a stereocomplexationable polymer blend with three different chemical structures. This novel stereocomplexation  or co-crystallization strongly suggests that an optically active polymer (l-configured or d-configured polymer) like optically active unsubstituted or substituted PLAs can act as "a configurational or helical molecular glue" for two oppositely configured optically active polymers (two d-configured polymers or two l-configured polymers) which cannot co-crystallize themselves to allow to co-crystallize in one SC crystalline lattice. The combination of l-configured polymer as a configurational or helical molecular glue with at least two d-configured polymers and vice versa will provide a novel way of designing polymeric composites, wherein SC-type co-crystallization will enhance the mechanical properties as reported for L-PLA/D-PLA homo-stereocomplex [11][12][13][14][15][16][17] , and physical properties, and biodegradation rate and behavior can be minutely manipulated.

Results and Discussion
Wide-angle X-ray diffractometry. For the estimation of crystalline species, interplanar distance (d), and crystallinity (X c ) of the blends, wide-angle X-ray diffractometry (WAXD) was performed. Figure 3(a,b) show the WAXD profiles of the blends crystallized by precipitation and solvent evaporation and Fig. 3(c,d) are those magnified in the 2θ range of 8.5-12.5°. The shown ratios in the figure are those of D-PLA/L-P2HB/D-P2H3MB (mol/mol/mol). For precipitated 0/50/50 blend, i.e., precipitated L-P2HB/D-P2H3MB 50/50 blend, L-P2HB/D-P2H3MB HTSC crystalline peaks were observed at 10.2, 17.7, 18.5, and 20.4° 73,74 and D-P2H3MB and L-P2HB homo-crystalline peaks were seen at 13.8 and 14.9°, respectively 22 . For solvent evaporated 0/50/50 blend, in addition to L-P2HB/D-P2H3MB HTSC crystalline peaks which appeared at the 2θ values similar to those of precipitated 0/50/50 blend, D-P2H3MB homo-crystalline peaks appeared at 12.9 and 14.0°2 2 and no L-P2HB homo-crystalline peak was observed. Such two different series of 2θ values were observed for D-P2H3MB homo-crystallites depending on the crystallization method of neat D-P2H3MB samples such as solvent evaporation and melt-crystallization 22 . The precipitated neat D-P2H3MB had the similar diffraction pattern with that reported for melt-crystallized neat D-P2H3MB 22  For the ternary D-PLA/L-P2HB/D-P2H3MB blends (red profiles in Fig. 3), which were composed of two d-configured polymers and one l-configured polymer, in addition to the D-PLA and D-P2H3MB homo-crystalline peaks, a new crystalline peak appeared at around 10.5° and its peak intensity increased with increasing L-P2HB content [ Fig. 3(c,d)]. This new crystalline peak was located between the main crystalline peaks of D-PLA/L-P2HB HTSC crystallites (broken lines) and L-P2HB/D-P2H3MB HTSC crystallites (dotted lines) in 50/50/0 and 0/50/50 blends, respectively, and was not observed for D-PLA, L-P2HB, and D-P2H3MB homo-crystallites. These results strongly suggest that the peak at around 10.5° for the ternary polymer blends can be ascribed to SC crystallites. As seen in magnified WAXD profiles [ Fig Also, the crystalline peak observed at around 21.1° became higher with increasing L-P2HB content, i.e., decreasing D-P2H3MB content in ternary polymer blends. At low L-P2HB contents or high D-P2H3MB contents, the crystalline peak observed at around 21.1° can be ascribed to D-P2H3MB homo-crystallites, whereas for a high L-P2HB content or a low D-P2H3MB content, this peak cannot be attributed to D-P2H3MB homo-crystallites or other homo-crystallites but can be ascribed to SC crystallites. Normally, other SC crystalline peaks can be observed in the 2θ range of 10.5-21.1°. However, there were many intense crystalline peaks in this 2θ range, other SC crystalline peaks should have been contained in or overlapped with other intense crystalline peaks and, therefore, other SC crystalline peaks could not be observed in the 2θ range of 10.5-21.1°, independently. With an increase in L-P2HB content, the D-P2H3MB homo-crystalline peaks at 13.8 and 24.0° and D-PLA homo-crystalline peak at 16.8° became smaller in the precipitated ternary blends, and the D-P2H3MB homo-crystalline peaks at 9.8, 12.9 and 13.8° and D-PLA homo-crystalline peak at 16.8° got smaller in the solvent evaporated ternary blends. These results support the SC formation in the ternary blends. The crystalline peaks observed at 14.8° for precipitated 30/40/30 and 25/50/25 blends can be ascribed to L-P2HB homo-crystallites.
The d values of SC crystallites in ternary polymer blends for 2θ range of 8.5-12.5° were estimated from the WAXD profiles in Fig. 3 and are plotted in Fig. 4(a) and (b) as a function of L-P2HB content. Due to strong overlapping of SC crystalline peak and D-P2H3MB homo-crystalline peak, d could not be estimated for solvent evaporated blends at L-P2HB content of 10 mol%. As seen in The X c values of blends were estimated from the WAXD profiles in Fig. 3. The thus obtained X c values are summarized in Table S1 in Supporting Information and those of 50/0/50 and ternary blends are plotted in Fig. 4 Differential scanning calorimetry. For the estimation of thermal properties of the blends, differential scanning calorimetry (DSC) was carried out (Fig. 5). The thermal properties estimated from the DSC thermograms in Fig. 5 are summarized in Table S2   D-P2H3MB homo-crystallites, a new melting peak appeared at around 200 °C and its intensity or area increased with increasing L-P2HB content, indicating this peak is attributable to the melting of SC crystallites.

Discussion
The SC-type crystalline peaks in WAXD profiles (Fig. 3) and crystallinity of SC-type crystallites [ Fig. 4(c) and (d)] of the ternary polymer blends increased with an increase in L-P2HB content. Furthermore, for the ternary polymer blends, the new higher melting peak appeared in DSC thermograms and its intensity or area increased with increasing L-P2HB content (Fig. 5). These results indicate the formation of SC crystallites in ternary polymer blends. In the ternary polymer blends, two types of HTSC crystallites, i.e., D-PLA/L-P2HB HTSC crystallites and L-P2HB/D-P2H3MB HTSC crystallites can be formed. As evident from Fig. 3 Table 1 tabulates the reported SCs of unsubstituted and substituted PLAs, together with the types of polymer chain and chemical structure. Previously, we reported HTSC, ternary stereocomplex, and quaternary stereocomplex formation of two, three, and four homopolymers, respectively, but these SCs comprise the optically active homopolymers with up to only two different chemical structures. However, as evident from Table 1, this article reports for the first time SC formation from optically active homopolymers with three different chemical structures.
For the 2θ range of 8.5-12.5°, the d values of ternary stereocomplex crystallites in the precipitated ternary blends were slightly closer to the d value of L-P2HB/D-P2H3MB HTSC crystallites than that of D-PLA/L-P2HB HTSC crystallites, whereas the d values of ternary stereocomplex of the solvent evaporated ternary blends was much closer to the d value of L-P2HB/D-P2H3MB HTSC crystallites than that for D-PLA/L-P2HB HTSC crystallites [ Fig. 4(a) and (b)]. These results are indicative of the fact that ternary stereocomplex crystallites contain a higher amount of larger sized d-configured D-P2H3MB and a lower amount of small sized d-configured D-PLA and the attractive force of l-configured L-P2HB during precipitation and solvent evaporation acted correspondingly slightly and much stronger for d-configured D-P2H3MB than for d-configured D-PLA. These results are consistent with the fact that HTSC formation occurs readily between L-P2HB and D-P2H3MB compared to that between D-PLA and L-P2HB 71-74 . Here, we must consider the probability that not l-configured L-P2HB but d-configured D-P2HB having the same configuration with that of d-configured D-PLA and D-P2H3MB may act a glue and form the co-crystallites in D-PLA/D-P2HB/D-P2H3MB ternary polymer blends. To exclude the probability, all d-configured ternary D-PLA/D-P2HB/D-P2H3MB (25/50/25) blends (abbreviated as D/D/D blends) were prepared and their crystallization behavior was investigated by WAXD and DSC. The obtained WAXD profiles and DSC thermograms are shown in Fig. 6, together with those of ternary D-PLA/L-P2HB/D-P2H3MB (25/50/25) blends (abbreviated as D/L/D blends) for reference. It is evident that the crystalline diffraction peaks in WAXD profiles and melting peak in DSC thermograms, which are attributable to a new type of co-crystallites, were not observed for all d-configured D/D/D blends. This result confirms that the only l-configured L-P2HB can attract d-configured D-PLA and D-P2H3MB and facilitate co-crystallization of d-configured D-PLA and D-P2H3MB to form ternary stereocomplex crystallites.
This article reports a very interesting result that l-configured L-P2HB attracts d-configured D-PLA and D-P2H3MB, which will not co-crystallize in a crystalline lattice without l-configured L-P2HB, to co-crystallize into ternary stereocomplex crystallites. Since, l-configured L-PLA have the helical structure with its direction opposite with that of d-configured D-PLA in homo-stereocomplex crystallites 18 , l-configured substituted PLAs, L-P2HB and P(L-2H3MB), are expected to have the helical structures with their directions opposite to d-configured substituted PLAs, D-P2HB and D-P2H3MB. Therefore, the results obtained in the present article strongly suggests that an optically active polymer (l-configured or d-configured polymer) like optically active unsubstituted or substituted PLAs can act as a configurational or helical molecular glue for two oppositely  configured optically active polymers (two d-configured polymers or two l-configured polymers) which cannot co-crystallize themselves to allow to co-crystallize in one ternary stereocomplex crystalline lattice, as schematically illustrated in Fig. 7. The structure of ternary stereocomplex here can be regarded as cardboard boxes (composed of three L-P2HB chains) which can house slightly different sized bottles (one D-PLA or D-P2H3MB chain) and shield two types of D-polymers. However, the present system differs from the so-called "unbalanced packing of chiral low molecular weight molecules" 93,94 which associates one L-isomer with two D-isomers (all of the same species) and has three entities with a fixed ratio of one to two in the unit-cell. The increased degree of freedom in polymer combination in the present study is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers. The synthesized polymers were purified by reprecipitation using chloroform and methanol (both JIS special grade, Nacali Tesque Inc.) as the solvent and nonsolvent, respectively. The purified polymers were dried under reduced pressure at least 6 days. Ternary or binary polymer blends were prepared by the procedure stated in the previous papers 11,19,71,85,87 . Briefly, each solution of the three or two polymers was prepared separately to have a polymer concentration of 1.0 g dL −1 and then admixed with each other under vigorous stirring. Dichloromethane (JIS special grade, Nacali Tesque Inc.) was used as the solvent. The mixed solution was cast onto a petri-dish, followed by solvent evaporation at 25 °C for approximately one day. The obtained blends were further dried under reduced pressure at least 6 days. The precipitated blends were obtained by dissolving solution-cast blends using dichloromethane as the solvent to have a polymer concentration of 10 g dL −1 and reprecipitation with stirred methanol as the nonsolvent. The volume ratio of blend solution and methanol 0.5/30 (mL/mL). The precipitated blends were rinsed with fresh methanol twice and dried under reduced pressure for at least 6 days.

Method
Physical measurements and observation. The weight-and number-average molecular weights (M w and M n , respectively) of the polymers were evaluated in chloroform at 40 °C using a Tosoh (Tokyo, Japan) gel permeation chromatography system with two TSK gel columns (GMH XL ) and polystyrene standards. Therefore, the M w and M n values are given relative to polystyrene. The specific optical rotation ([α] 25 589 ) of the polymers was measured in chloroform at a concentration of 1 g dL −1 and 25 °C using a JASCO (Tokyo, Japan) P-2100 polarimeter at a wave length of 589 nm. The glass transition, cold crystallization, and melting temperatures (T g , T cc , and T m , respectively) and the enthalpies of cold crystallization and melting (ΔH cc and ΔH m , 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 . The samples (ca. 3 mg) were heated from 0 to 250 °C at a rate of 10 °C min −1 . Wide-angle X-ray diffractometry was carried out at 25 °C using a RINT-2500 (Rigaku Co., Tokyo, Japan) equipped with a Cu-Kα source [wave length (λ ) = 1.5418 Å]. Molecular characteristics of the polymers used in the present study are shown in Table 2.