Synthesis of pH-responsive statistical polyampholytes by PET-RAFT polymerization of protected monomers

Abstract

Synthetic polymers have emerged as powerful models for investigating drivers of liquid–liquid phase separation in biological materials. However, synthesizing polymers with “protein-like” distributions of cationic, anionic, hydrophilic, hydrophobic, and aromatic sidechains has remained a significant challenge. Here, we demonstrate that this problem can be addressed by polymerizing protected amine- and acid-functionalized monomers, along with a wide variety of nonionic comonomers, under photoinduced electron/energy transfer reversible addition–fragmentation chain transfer polymerization (PET-RAFT) conditions. We show that PET-RAFT enables controlled polymerization of tert-butyl (2-acrylamidoethyl)carbamate (Boc-AEAm) and tert-butyl acryloylglycinate (tBu-AG). Copolymerization of these monomers proceeds with reactivity ratios close to one, and deprotection with trifluoroacetic acid yields polyampholytes with pH-dependent phase behavior consistent with expected changes in the polymers’ isoelectric points as the cation : anion ratio is varied. We further show that a 50 : 50 mixture of these monomers can be copolymerized with hydrophilic (acrylamide, hydroxyethyl acrylamide), hydrophobic (n-butyl acrylamide), and aromatic (benzyl acrylamide) comonomers, which in turn significantly impact the pH-dependent phase behavior of the materials. This approach is both high-throughput and scalable, and promises to offer new opportunities both for understanding composition–property relationships in polyampholyte materials and for preparing polyampholytes with targeted properties and functions for a wide range of applications.