Design, Synthesis And Characterization Of Linear-Dendron-Like Biodegradable Block Co-polymers

Based on biodegradable polyester PCL as precursor, combining PEO orPBLG and introducing the "asymmetry” concept, we obtained a series oflinear-dendron-like biodegradable block copolymers. The crystallization andself-assembly property were in detail characterized.(1) Synthesis and Characterization of Linear-Dendron-likePCL-b-PEO Copolymers via the Combination of Ring-OpeningPolymerization and Click ChemistryA new class of linear-dendron-like PCL-b-PEO copolymers wassynthesized via controlled ring-opening polymerization (ROP) of-caprolactone(CL) followed by a click conjugation with azide-terminated PEO (PEO-N3). Thedendron-like PCL terminated with a clickable alkyne group (Dm-PCL, m=0,1,2, and3) was for the first time synthesized from the ROP of CL monomer usinga propargyl focal point dendrons (Dm) as the initiators and stannous octoate ascatalyst in bulk at130℃. Then, the linear-dendron-like PCL-b-PEO copolymers(Dm-PCL-b-PEO) were obtained by the click conjugation of Dm-PCL withPEO-N3using PMDETA/CuBr in DMF solution at35℃. Their molecularstructures and physical properties were in detail characterized by FT-IR, NMR,MALLS-GPC, DSC, WAXD, and POM. Moreover, the biodegradable micellesand vesicles with different sizes (less than100nm) were easily fabricated fromthese PCL-b-PEO copolymers in aqueous solution, and both the PEOcomposition and the linear-dendron-like architecture of copolymers controlledthe morphology and the average size of self-assembled nanoparticles.(2) A Versatile Strategy for the Synthesis of Dendron-likePolypeptide/Linear Poly(-caprolactone) Block Copolymers via ClickChemistryA dendron-like polypeptide/linear poly(-caprolactone) block copolymerswith asymmetrical topology (i.e., dendron-like PBLG/linear PCL copolymershaving2~mPBLG branches, m=0,1,2, and3; denoted as PCL-Dm-PBLG) wasfor the first time synthesized via the combination of controlled ROP of -caprolactone, click chemistry, and the ROP of γ-benzyl-L-glutamateN-carboxyanhydride (BLG-NCA). The linear hydroxyl-terminated PCL(PCL-OH) was synthesized by controlled ROP of-caprolactone and thentransformed into clickable azide-terminated PCL (PCL-N3). The PCL-N3precursor was further click conjugated with propargyl focal pointPAMAM-typed dendrons (i.e., Dm having2~m primary amine groups) togenerate PCL-dendrons (PCL-Dm) using CuBr/PMDETA as catalyst in DMFsolution at35℃. Finally, PCL-Dm was used as macroinitiator for the ROP ofBLG-NCA monomer to produce the targeted PCL-Dm-PBLG block copolymers.Their molecular structures and physical properties were characterized in detailby FT-IR, NMR, MALDI-TOF-MS, GPC, DSC, and WAXD.To the best of our knowledge, this is the first report that describes thesynthesis of Linear-dendron-like PCL based copolymers with asymmetricaltopology via the combination of ROP and click chemistry. Consequently, thisprovides a versatile strategy for the synthesis of biodegradable and biomimeticpolyester based biohybrids.