Synthesis of amphiphilic dendronized block copolypeptides and their properties

A series of novel amphiphilic block copolypepides bearing the hydrophilic second-generation (G2) dendritic ether grafts denoted as PBLG-b-(PELG-g-G2) were designed and synthesized by a combination of ring-opening polymerization and click chemistry. First, azido-terminated poly(γ-benzyl-L-glutamate)s (PBLG) with different molecular weights were synthesized by ring-opening polymerization of γ-benzyl-L-glutamate-Ncarboxyanhydride (BLG-NCA) in DMF at room temperature using 3-azido-1-propanamine as initiator and alkyne-terminated poly(γ-2-chloroethyl-L-glutamate) (PCELG) was synthesized by ring-opening polymerization of γ-2-chloroethyl-L-glutamate-N-carboxyanhydride in DMF at room temperature using propargylamine as initiator. The block copolypeptides poly(γ-benzyl-L-glutamate)-block-poly(γ-2-chloroethyl-L-glutamate) (PBLGb-PCELG) bearing chloride side groups were synthesized by click chemistry with high efficiency from the azido-terminated PBLG and the alkyne-terminated PCELG in the presence of CuBr and 1, 1, 4, 7, 7-pentamethyldiethylenetriamine (PMDETA) catalyst system. Then, PBLG-b-PCELG containing chloride side groups was subsequently reacted with excessive sodium azide in DMF to yield a block copolypeptide bearing azido side groups denoted as PBLG-b-(PNELG). The hydrophilic second-generation (G₂) dendritic ethers were finally grafted to the side chains of the block copolypeptides PBLG-b-(PNELG) by click chemistry in the presence of CuBr/PMDETA catalyst system and the amphiphilic dendronized block copolypepides PBLG-b-(PELG-g-G₂) were successfully synthesized. Their molecular structures were further characterized by 1H-NMR, FTIR and GPC. The thermo-responsive behaviour of PBLG-b-(PELG-g-G₂) in water were investigated using UV-Vis and the results showed that the values of the cloud point temperatures (TCP) of PBLG-b-(PELG-g-G₂) became lower with the length increase of the hydrophobic PBLG chain segment. This was explained by the fact that the amphiphilic block copolypeptides PBLG-b-(PELG-g-G₂) in water self-assembled into core-shell micelles with the hydrophobic PBLG as the core and the hydrophilic dendronized polypeptide segment as the shell. The degree of hysteresis, defined as the difference in the cloud points upon heating and cooling, in each system lowered with the decrease in amphiphilic block copolypepide concentrations for micelles. The synthesized PBLG-b-(PELG-g-G2) may be expected to have good application prospects in the biomedical field due to the excellent biocompatibility of their structural units.