Core-Shell Molecular Bottlebrushes with Helical Polypeptide Backbone: Synthesis, Characterization, and Solution Conformations

A series of core shell molecular bottlebrushes with helical polypeptide backbone and polylactide-b-poly-(ethylene glycol) block copolymer side chains [PPLG-g.(PLA-b-PEG)] have been synthesized via a grafting-to method. The structurally well-defined side chains with low molecular weight distribution (PDI < 1.03) have been synthesized by ring-opening polymerization (ROP) of DL-lactides using PEG-OH macroinitiator and AlEt3 catalyst. Postpolymerization modification by esterification enables the quantitative installation of an alkynyl functionality at the block polymer chain ends. Grafting of alkynyl-terminated PLA-b-PEG onto poly(gamma-azidopropyl-L-glutamate) (PAPLG) via copper mediated [2 + 3] alkyne-azide 1,3 dipolar cycloaddition yields the targeted molecular bottlebrushes with high grafting density under mild conditions. A combination of the Langmuir-Blodgett (LB) technique with atomic force microscopy (AFM) has allowed for direct imaging of the synthesized molecular brushes and characterization of their molecular weight (MW) distribution. The imaged individual macromolecules demonstrate a wormlike conformation with an average length shorter than the contour length of the backbone. In agreement with the AFM observations, circular dichroism (CD) studies of PPLG-g(PLA-b-PEG) in aqueous solution reveal that all molecular bottlebrushes retain backbones with alpha-helical conformations in acidic or neutral conditions. Longer side chains destabilize the helical conformations due to enhanced steric hindrance. Temperature variation can cause partial and reversible unfolding of the helical backbones. The temperature effect is greatly diminished for the bottlebrushes with longer side chains.