*4.1. PLA*/α*-Cyclodextrins*

Threading α-cyclodextrin molecules onto PLA chains results in the formation of supramolecular inclusion complexes, organized by non-covalent interactions [109–111]. The formation of stable poly(pseudo)rotaxanes was reported when α-CD was threaded onto PLLA chains and PLLA-PEG-PLLA triblock copolymers of di fferent molar ratios of [LA]/[PEG] (Tri-1: 23, Tri-2: 31, Tri-3: 45, Tri-4: 54) [110]. For poly(pseudo)rotaxanes of both kinds, threaded onto triblock copolymers or on PLLA, the stoichiometric number of [LA] monomer units and [CD] was found to be 2:1. The complexation strongly reduced the solubility of the polymers.

13C CP/MAS NMR studies in the solid state indicated that α-CD in such polymeric IC adopted more symmetric cyclic conformations, which influenced the splitting of all the C1-6 glucose carbon resonances of the cyclodextrin moieties (Figure 22) [110]. The signals characteristic of the glycoside linkage (98 ppm and 80 ppm) disappeared in the spectra of channel-structured IC. The most symmetric cyclic conformations of α-CD were adopted in the inclusion complex with a 2:1 feed ratio. More evidence of IC formation may be obtained by FTIR spectroscopy. A shift of the ν (O-H) mode to higher frequencies can be observed (3389 cm<sup>−</sup><sup>1</sup> for pure α-CD and 3420 cm<sup>−</sup><sup>1</sup> for IC) due to the association of OH groups with the gues<sup>t</sup> polymeric chains [110]. The stretching band ν (C-H) (300–2950 cm<sup>−</sup>1) in α-CD was also shifted.

**Figure 22.** Solid-state 13C CP/MAS NMR spectra of R-CD (**a**) and inclusion complexes of PLLA/α-CD (**b**), Tri-1/α-CD (**c**), and Tri-4/α-CD (**d**) [110]. Reprinted with permission from Macromolecules. Copyright (2003), American Chemical Society.

The formation of IC with α-CD was confirmed by wide-angle X-ray di ffraction measurements (exemplary di ffractograms are shown in Figure 23). The WAXS patterns of PLA-IC are di fferent from those of PLA and α-CD. A new channel-type crystal structure was formed with the copolymers confined to CD, and the components lost their original crystalline features. The X-ray di ffractograms of PLLA/α-CD and the Tri-1/α-CD inclusion complexes showed patterns di fferent from those of host CD and gues<sup>t</sup> macromolecules [110]. A set of reflections at 2θ = 7.60◦ (*d* = 11.6 Å), 13.0◦ (*d* = 6.80 Å), and 20.0◦ (*d* = 4.44 Å) indicated the formation of a columnar crystalline structure (a hexagonal unit cell with the lateral dimension *a* = 13.6 Å). The strong 210 reflection (2θ = 20.0◦) is characteristic of the channel structure of IC crystals containing α-CD (the electron density distribution of the core of α-CD molecules with a radius of about 5 Å) [110,111].

**Figure 23.** X-ray diffraction patterns for α-CD (**a**), PLLA (**b**), poly(ethylene glycol) (PEG)/α-CD inclusion complex (**c**), PLLA/α-CD inclusion complex (**d**), and Tri-1/α-CD inclusion complex (**e**) [110]. Reprinted with permission from Macromolecules. Copyright (2003), American Chemical Society.

Dielectric relaxation spectroscopy (DRS) studies on poly(D,L-lactic acid) (PDLLA) and its inclusion complexes in α-CD of various ratios of incorporated/initial PDLLA revealed a distinguishably different dynamical response of the PDLLA chains constrained between α-CD from the fraction of macromolecules incorporated inside the channels (Figure 24) [112]. The presence of α-CD molecules depletes the segmental α-process and resolves two sub-Tg relaxations. The cooperative motions (α-relaxation) are supressed for PDLLA hosted inside the channels whereas the relaxation of macromolecules situated between α-CD channels is reduced and shifts to higher temperatures (~4.5 ◦C). A secondary relaxation—the Johari–Goldstein process (βJG-process)—that can be related to the PDLLA confinement effect was also observed in the IC. An additional secondary γ process of length scale inferior to inter- or intra-channel dimensions was detected only in the inclusion complexes.

**Figure 24.** Isochronal (IC) plot of the imaginary part of the complex permittivity at 1 kHz for poly(<sup>d</sup>,<sup>l</sup>-lactic acid) (PDLLA) (•), IC1 (-), and IC2 (). The ratios of incorporated/initial PDLLA by weight percentage (%, *w*/*w*) were 10/24 (IC1) and 15/46 (IC2) [112]. Reprinted with permission from The Journal of Physical Chemistry B. Copyright (2014), American Chemical Society.

The optically active CDs are known for their ability to recognize chiral molecules [113–115]. Interestingly, Ohya et al. reported that the inclusion complex of α-cyclodextrin with PLLA is preferentially formed compared to that with poly(d-lactide) (PDLA) (Scheme 11) [116]. The recognition of PDLA chains was significant, and they were almost excluded by α-CD. The phenomenon was

confirmed by tests with (ll)- and (dd)-lactic acid dimer methyl esters. Only (LL) species formed IC with α-CD. The crystalline structures of PLLA/α-CD and PDLA/α-CD were investigated by DSC and X-ray diffraction (Figure 25). The WAXS diagrams of PLLA, PDLA, and PDLA/α-CD featured intensive peaks at 2θ = 17◦ and 19◦ (typical for α-crystals of polylactide). PDLA/α-CD showed a melting point around 160 ◦C (similarly to neat PLLA or PDLA), indicating a crystalline nature of the sample. The diffraction pattern for PLLA/α-CD was characteristic for IC with a columnar structure (2θ = 20◦).

**Scheme 11.** (**a**) Chiral recognition of polylactides by α-CD, and (**b**) preparation of PLA/α-CD inclusion complex [116]. Reprinted with permission from Macromolecules. Copyright (2007), American Chemical Society.

**Figure 25.** Wide-angle X-ray diffraction patterns of PLLA, PLLA/R-CD poly(D-lactide) (PDLA) and PDLA/R-CD [116]. Reprinted with permission from Macromolecules. Copyright (2007), American Chemical Society.

Experiments with triblock copolymers—PLLA-PEG-PLLA and PDLA-PEG-PDLA—showed that α-CD molecules were hosting PEG segments irrespectively of the enantiomeric form of the polylactide blocks. It suggests that α-CD can freely slide along the PDLA segments and that the fitting between the polymer width and diameter of the CD cavity is not the only factor that governs the IC formation. It was therefore concluded that the reason for the chiral recognition is not the polymer chain steric hindrance (similar for PLLA and PDLA) but the thermodynamic stability of the diastereomeric IC. Chiral fitting with the α-CD cavity is more favourable to PLLA and allows the linking of several cyclodextrine molecules through hydrogen bonds. The molecules of α-CD have to rotate unidirectionally on sliding down the helical chain of PLLA. This phenomenon may be exploited for the design of molecular motors.

The α-CD host polylactide gues<sup>t</sup> IC with a channel-type structure had different thermal characteristics to the parent polylactide [109–111]. No cold crystallization and melting can be detected if the PLA chains are included inside the α-CD voids (Figure 26). Small amounts of IC may exert a nucleation effect and promote the crystallization of the PLA matrix during both the non-isothermal

and isothermal crystallization experiments [111]. Upon cooling from melt (5 ◦C/min), an exotherm was observed at about 94 ◦C, suggesting that IC particles can accelerate the nucleation. If the PLA contained free α-CD (not IC) then the nucleation effect was small. It was also noted that α-CD may act as a nucleating agen<sup>t</sup> for the crystallization of PLLA from the solution with the formation of spherulitic structures [117]. The size of the spherulites in the cast film depended on the amount of α-CD and the casting rate. Very small crystallites were formed in the presence of IC and on fast casting.

**Figure 26.** DSC traces of α-CD, PLA, and PLA-IC during heating at 10 ◦C/min [111]. Reprinted with permission from Springer Nature: Polymer Bulletin. Copyright (2013).
