One-Step Synthesis of Sequence-Defined Polypeptide-block-polyester by Lewis Pair-Catalyzed Chemo-Selective Copolymerization

Polypeptide-block-polyester copolymers exhibited diversified physicomechanical properties, improved biocompatibility and degradability, as well as multiple functionalities. Such copolymers were mostly synthesized by macroinitiators or a sequential addition method, generally requiring multiple modification/isolation/purification/addition steps. There is only one example for the synthesis of polypeptide-based block copolymers from heterocyclic mixtures via redox-switchable copolymerization under external stimuli. In this work, we established a chemo-selective process (without external stimuli) and successfully synthesized sequence-controlled polypeptide-block-polyester copolymers from N-carboxyanhydride (NCA)/L-lactide (L-LA) mixtures. The ZnR2/base pairs, exhibiting good control in both NCA and L-LA polymerizations, were used to catalyze the chemo-selective copolymerization. Kinetic studies and density functional theory calculations suggested that the excellent chemo-selectivity derived from the preferential attack of primary amine chain end to NCA with intrinsically high reactivity. In addition, there was a dormant period between the two polymerization cycles. This feature increased the degree of monomer sequencing and block resolution. Different polypeptide-b-polylactide block copolymers were readily prepared by varying monomer structure, feed ratio, and initiator, providing a powerful toolbox for creating various advanced polypeptiede-base materials for many different applications.