Sequential crystallization and morphology of triple crystalline biodegradable PEO-b-PCL-b-PLLA triblock terpolymers

et al.The sequential crystallization of poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(l-lactide) (PEO-b-PCL-b-PLLA) triblock terpolymers, in which the three blocks are able to crystallize separately and sequentially from the melt, is presented. Two terpolymers with identical PEO and PCL block lengths and two different PLLA block lengths were prepared, thus the effect of increasing PLLA content on the crystallization behavior and morphology was evaluated. Wide angle X-ray scattering (WAXS) experiments performed on cooling from the melt confirmed the triple crystalline nature of these terpolymers and revealed that they crystallize in sequence: the PLLA block crystallizes first, then the PCL block, and finally the PEO block. Differential scanning calorimetry (DSC) analysis further demonstrated that the three blocks can crystallize from the melt when a low cooling rate is employed. The crystallization process takes place from a homogenous melt as indicated by small angle X-ray scattering (SAXS) experiments. The crystallization and melting enthalpies and temperatures of both PEO and PCL blocks decrease as PLLA content in the terpolymer increases. Polarized light optical microscopy (PLOM) demonstrated that the PLLA block templates the morphology of the terpolymer, as it forms spherulites upon cooling from the melt. The subsequent crystallization of PCL and PEO blocks occurs inside the interlamellar regions of the previously formed PLLA block spherulites. In this way, unique triple crystalline mixed spherulitic superstructures have been observed for the first time. As the PLLA content in the terpolymer is reduced the superstructural morphology changes from spherulites to a more axialitic-like structure.We gratefully acknowledge funds received through the following projects: “MAT2014-53437-C2-P, MAT2012-31088 (Spanish-MINECO and EU)”, UPV/EHU (UFI 11/56) and GIC IT-586-13, IT-654-13 (Basque Government).Peer Reviewe

Well-defined homopolypeptides, copolypeptides, and hybrids of Poly(l-proline)

l-Proline is the only, out of 20 essential, amino acid that contains a cyclized substituted α-amino group (is formally an imino acid), which restricts its conformational shape. The synthesis of well-defined homo- and copolymers of l-proline has been plagued either by the low purity of the monomer or the inability of most initiating species to polymerize the corresponding N-carboxy anhydride (NCA) because they require a hydrogen on the 3-N position of the five-member ring of the NCA, which is missing. Herein, highly pure l-proline NCA was synthesized by using the Boc-protected, rather than the free amino acid. The protection of the amine group as well as the efficient purification method utilized resulted in the synthesis of highly pure l-proline NCA. The high purity of the monomer and the use of an amino initiator, which does not require the presence of the 3-N hydrogen, led for the first time to well-defined poly(l-proline) (PLP) homopolymers, poly(ethylene oxide)-b-poly(l-proline), and poly(l-proline)-b-poly(ethylene oxide)-b-poly(l-proline) hybrids, along with poly(γ-benzyl-l-glutamate)-b-poly(l-proline) and poly(Boc-l-lysine)-b-poly(l-proline) copolypeptides. The combined characterization (NMR, FTIR, and MS) that results for the l-proline NCA revealed its high purity. In addition, all synthesized polymers exhibit high molecular and compositional homogeneity

Direct Identification of Three Crystalline Phases in PEO-b-PCL-b-PLLA Triblock Terpolymer by In Situ Hot-Stage Atomic Force Microscopy

Unformatted preprint version of the submitted articleIn this work, we provide a detailed description of the tri-lamellar nanoscale morphology of a triple crystalline PEO-b-PCL-b-PLLA triblock terpolymer obtained by Hot-Stage Atomic Force microscopy (AFM) imaging and Wide Angle X-ray scattering (WAXS) analysis for the first time. The precursor PCL-b-PLLA diblock copolymer has also been included in the study for comparison purposes. A two-step crystallization protocol has been applied to create a distinct lamellar morphology. Both WAXS and AFM revealed the double crystalline nature of the diblock copolymer. However, the identification of multiple crystalline phases in the triblock terpolymer by AFM and WAXS at room temperature is not straightforward. The advantages of hot-stage AFM allowed following the evolution of the lamellar morphology and the successive melting of the tricrystalline PEO-b-PCL-b-PLLA sample during heating. Taking into account the melting temperature of each crystalline block, the existing lamellar populations were clearly identified. At 45 °C, the thinnest lamellae disappeared, due to the melting of PEO crystals. The medium size lamellae disappeared at 60 °C when PCL crystals melt. At that temperature, the only remaining crystals are those of the PLLA block. AFM mechanical modulus images provide further evidence of the lamellar self-assembly of the triblock terpolymer. The nanoscale arrangement includes lamellae of PCL, PEO, or both in between the PLLA lamellae. Hot-Stage AFM is a valuable technique to elucidate the morphological features of complex multi-crystalline systems.This work has received funding from the European Union´s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 778092, from MINECO, project: MAT2017-83014-C2-1-P and from the Basque Government through grant IT1309-19. We are grateful to the National Science Foundation of China (nos. 51773182, 51973202), The Young Out-standing Teachers of the University in Henan Province (2019GGJS003). N.H. acknowledges the support of King Abdullah University of Science and Technology (KAUST)

Generating Triple Crystalline Superstructures in Melt Miscible PEO-b-PCL-b-PLLA Triblock Terpolymers by Controlling Thermal History and Sequential Crystallization

The morphology, crystallization behavior and properties of multi-crystalline polymer systems based on triple crystalline biodegradable PEO-b-PCL-b-PLLA triblock terpolymers are reviewed. The triblock terpolymers, with increasing PLLA content, exhibited a triple crystalline nature. Upon cooling from melt, the PLLA block crystallizes first and templates the spherulitic morphology of the terpolymer. Then, the PCL block crystalizes and, lastly, the PEO block. These triblock terpolymers are probably melt miscible, as SAXS experiments confirmed. Thus, the crystallization of PCL and PEO blocks takes place within the interlamellar zones of the PLLA spherulites that were formed previously. Therefore, the lamellae of PLLA, PCL and PEO exist side-by-side within a unique spherulite, constituting a novel triple crystalline superstructure. The theoretical analysis of SAXS curves implies that only one lamella of either PCL or PEO can occupy the interlamellar space in between two contiguous lamellae of PLLA. Several complex competitive effects such as plasticizing, nucleation, anti-plasticizing and confinement take place during the isothermal crystallization of each block in the terpolymers. New results on how Successive Self-nucleation and Annealing (SSA) thermal treatment can be used as an additional suitable technique to properly separate the three crystalline phases in these triple crystalline triblock terpolymers are also included in this contribution.The POLYMAT/UPV/EHU team would like to acknowledge funding from MINECO through project: MAT2017-83014-C2-1-P, and from ALBA synchrotron facility. We also acknowledge funding by the European Union´s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 778092. The support of the National Key R&D Program of China (2017YFE0117800) is also gratefully acknowledged

Poly(Sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA)

Poly­(sarcosine) (PSar) is a non-ionic hydrophilic polypeptoid with numerous biologically relevant properties, making it an appealing candidate for the development of amphiphilic block copolymer nanostructures. In this work, the fabrication of poly­(sarcosine)-based diblock copolymer nano-objects with various morphologies via aqueous reversible addition–fragmentation chain-transfer (RAFT)-mediated photoinitiated polymerization-induced self-assembly (photo-PISA) is reported. Poly­(sarcosine) was first synthesized via ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride, using high-vacuum techniques. A small molecule chain transfer agent (CTA) was then coupled to the active ω-amino chain end of the telechelic polymer for the synthesis of a poly­(sarcosine)-based macro-CTA. Controlled chain-extensions of a commercially available water-miscible methacrylate monomer (2-hydroxypropyl methacrylate) were achieved via photo-PISA under mild reaction conditions, using PSar macro-CTA. Upon varying the degree of polymerization and concentration of the core-forming monomer, morphologies evolving from spherical micelles to worm-like micelles and vesicles were accessed, as determined by dynamic light scattering and transmission electron microscopy, resulting in the construction of a detailed phase diagram. The resistance of both colloidally stable empty vesicles and enzyme-loaded nanoreactors against degradation by a series of proteases was finally assessed. Overall, our findings underline the potential of poly­(sarcosine) as an alternative corona-forming polymer to poly­(ethylene glycol)-based analogues of PISA assemblies for use in various pharmaceutical and biomedical applications

Characterization of a 4-miktoarm star copolymer of the (PS-b-PI) 3 PS type by temperature gradient interaction chromatography

Abstract Temperature gradient interaction chromatography (TGIC) was applied for the separation of a complex miktoarm star copolymer which has one polystyrene (PS) arm and three polystyrene-b-polyisoprene (PS-b-PI) diblock copolymer arms. Such miktoarm star polymers are much more difficult to characterize than branched homopolymers since the byproduct, typically polymers with missing arm(s) or coupled products, have not only different molecular weights but also different compositions. TGIC was able to fully separate the byproducts, and the composition of the molecular species corresponding to the different separated elution peaks was determined by two methods, fractionation/NMR and multiple detection (UV and RI). A reasonable agreement between the results of the two methods was obtained. By using the composition found, the corresponding molecular weights were determined by multi-angle light scattering detection. Based on the composition and the molecular weight we were able to identify the structure of the different molecular species

Block Copolymers of Macrolactones/Small Lactones by a "Catalyst-Switch" Organocatalytic Strategy. Thermal Properties and Phase Behavior

Poly(macrolactones) (PMLs) can be considered as biodegradable alternatives of polyethylene; however, controlling the ring-opening polymerization (ROP) of macrolactone (ML) monomers remains a challenge due to their low ring strain. To overcome this problem, phosphazene (t-BuP_4), a strong superbase, has to be used as catalyst. Unfortunately, the one-pot sequential block copolymerization of MLs with small lactones (SLs) is impossible since the high basicity of t-BuP_4 promotes both intra- and intermolecular transesterification reactions, thus leading to random copolymers. By using ROP and the “catalyst-switch” strategy [benzyl alcohol, t-BuP_4/neutralization with diphenyl phosphate/(t-BuP_2)], we were able to synthesize different well-defined PML-b-PSL block copolymers (MLs: dodecalactone, ω-pentadecalactone, and ω-hexadecalactone; SLs: δ-valerolactone and ε-caprolactone). The thermal properties and the phase behavior of these block copolymers were studied by differential scanning calorimetry and X-ray diffraction spectroscopy. This study shows that the thermal properties and phase behavior of PMLs-b-PSLs are largely influenced by the PMLs block if PMLs components constitute the majority of the block copolymers

Block Copolymers of Macrolactones/Small Lactones by a "Catalyst-Switch" Organocatalytic Strategy. Thermal Properties and Phase Behavior

Poly(macrolactones) (PMLs) can be considered as biodegradable alternatives of polyethylene; however, controlling the ring-opening polymerization (ROP) of macrolactone (ML) monomers remains a challenge due to their low ring strain. To overcome this problem, phosphazene (t-BuP_4), a strong superbase, has to be used as catalyst. Unfortunately, the one-pot sequential block copolymerization of MLs with small lactones (SLs) is impossible since the high basicity of t-BuP_4 promotes both intra- and intermolecular transesterification reactions, thus leading to random copolymers. By using ROP and the “catalyst-switch” strategy [benzyl alcohol, t-BuP_4/neutralization with diphenyl phosphate/(t-BuP_2)], we were able to synthesize different well-defined PML-b-PSL block copolymers (MLs: dodecalactone, ω-pentadecalactone, and ω-hexadecalactone; SLs: δ-valerolactone and ε-caprolactone). The thermal properties and the phase behavior of these block copolymers were studied by differential scanning calorimetry and X-ray diffraction spectroscopy. This study shows that the thermal properties and phase behavior of PMLs-b-PSLs are largely influenced by the PMLs block if PMLs components constitute the majority of the block copolymers