Ester Functional Epoxide Monomers for Random and Gradient Poly(ethylene glycol) Polyelectrolytes with Multiple Carboxylic Acid Moieties

Abstract

The tailormade ester functional epoxides, methyl 4,5-epoxypentenoate (MEP) and tbutyl 4,5-epoxypentenoate (tBEP), were synthesized in good overall yields (60–65%) in short reaction sequences. Both MEP and tBEP were investigated as comonomers in the statistical copolymerization with ethylene oxide (EO) via the monomer-activated anionic ring-opening polymerization (MAROP), using triisobutyl-aluminum as a catalyst. Homopolymers and a series of copolymers of EO with varied molar contents of MEP and tBEP (0.6–31.3 mol %) were prepared, possessing molecular weights up to 11,800 g mol–1. Surprisingly, in situ 1H NMR kinetics studies revealed an ideally random copolymer microstructure for EO/MEP copolymers (rEO = 0.99, rMEP = 1.0) via MAROP for the first time. tBEP was found to be a less reactive comonomer, yielding gradient polyether structures (rEO = 2.9, rtBEP = 0.35). After polymerization, the ester-protecting groups were fully cleaved under basic or acidic conditions, respectively, resulting in either random or gradient distribution of carboxyl moieties. MTT assays demonstrated good biocompatibility of the novel carboxylic acid functional poly(ethylene glycol) (PEG) copolymers. The thermal properties of the copolymers were investigated via differential scanning calorimetry, showing the highly flexible nature of the PEG-based polyelectrolytes after deprotection. The liberated carboxylic acid groups were addressed with Ca2+ cations, resulting in cross-linked polymer networks.