Design and Synthesis of Thermoresponsive Degradable Copolymers: Integrating Hydroxy-Functional Vinyl Ethers with Cyclic Ketene Acetals

Abstract

Degradable copolymers with adjustable thermoresponsive characteristics are synthesized through radical copolymerization of hydroxy-functional vinyl ethers (OH-VEs), such as 2-hydroxyethyl vinyl ether (HEVE) or di(ethylene glycol) vinyl ether (DEGV), with 2-methylene-1,3-dioxepane (MDO). Mechanistic investigations, including reactivity ratio determination and ¹H NMR spectroscopy, reveal that hydrogen bonding from the hydroxy groups in vinyl ethers affects both radical vinyl polymerization of OH-VEs and radical ring-opening polymerization of MDO. The resulting poly(HEVE-co-MDO) and poly(DEGV-co-MDO) copolymers exhibit LCST-type thermoresponsive behavior in aqueous solutions within specific MDO composition ranges (23-28 mol% and 35-37 mol%, respectively), whereas poly(vinyl alcohol-co-MDO) without oxyethylene moieties remains either fully soluble or insoluble, irrespective of temperature. Poly(DEGV-co-MDO) uniquely forms coacervates in turbid solutions due to its enhanced hydrophilicity, a phenomenon not observed with poly(HEVE-co-MDO). RAFT polymerization facilitates molecular weight control, demonstrating an inverse relationship between molecular weight and cloud point temperature. The copolymers exhibit selective degradability of MDO units under alkaline conditions and are expected to demonstrate good biocompatibility, as suggested by cytotoxicity assays.