Synthesis of Arborescent Copolymers Based on Poly(γ-benzyl L-glutamate)
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The synthesis of arborescent poly(gamma-benzyl L-glutamate) (PBG) molecules was achieved through successive grafting reactions of linear PBG chains. These linear PBG building blocks were obtained by the ring-opening polymerization of gamma-benzyl L-glutamic acid N-carboxyanhydride initiated with n-hexylamine. Cleavage of a fraction of the benzyl ester groups on a linear PBG substrate, followed by coupling with linear PBG side chains via standard peptide coupling techniques, yielded a comb-branched or generation zero (G0) arborescent PBG. Further cycles of partial deprotection and grafting reactions led to arborescent PBG molecules of the subsequent generations (G1-G3). Molecular weights reaching over 106 were obtained for G3 arborescent PBG, while maintaining narrow molecular weight distributions (Mw/Mn ≤ 1.06) for each generation. The arborescent PBG molecules displayed α-helix to randomly coiled chain conformation changes from N,N-dimethylformamide to dimethylsulfoxide. Amphiphilic copolymers were obtained by grafting the arborescent PBG substrates randomly with side chains of either poly(glycidol acetal), poly(ethylene oxide), or poly(γ-tert-butyl L-glutamate) via the same peptide coupling techniques used to generate arborescent PBG. Copolymers were also synthesized by a chain end grafting method, whereby the linear chain segments were coupled exclusively with the chain termini of the arborescent PBG substrates. Water-soluble species were obtained by removal of the acetal and tert-butyl protecting groups from the poly(glycidol acetal) and poly(γ-tert-butyl L-glutamate) side chains, respectively, while the copolymers with poly(ethylene oxide) side chains did not require further modifications. Dynamic light scattering (DLS) measurements on the arborescent copolymers in aqueous solutions revealed that unimolecular micelles were the dominant species for the chain end grafted arborescent copolymers, whereas the randomly grafted arborescent copolymers were either insoluble or displayed significant aggregation. The synthesis of arborescent copolymers with PBG cores was also achieved through “click” chemistry, using the copper-catalyzed azide-alkyne Huisgen cycloaddition (CuAAC) reaction. To that end, polyglycidol, poly(ethylene oxide), and poly(2-trimethylsilylethyl acrylate) chains terminally functionalized with azide groups were grafted onto either randomly or chain end alkyne-functionalized arborescent PBG substrates. DLS analysis revealed solubility trends similar to the arborescent copolymers obtained by the peptide coupling method. The CuAAC reaction enables the incorporation of a broader range of polymers into arborescent copolymer structures derived from PBG substrates.