A Vinyl Ether-Functional Polycarbonate as a Template for Multiple Postpolymerization Modifications

摘要

A highly-reactive vinyl ether-functionalized aliphatic polycarbonate and its block copolymer were developed as templates for multiple post-polymerization conjugation chemistries. The vinyl ether-functional six-membered cyclic carbonate monomer was synthesized by a well-established two-step procedure starting from 2,2-bis(hydroxymethyl)propionic acid. An organobase-catalyzed ring-opening polymerization of the synthesized monomer afforded polycarbonates with pendant vinyl ether functionalities (PMVEC). The vinyl ether moieties on the resulting polymers were readily conjugated with hydroxyl- or thiol-containing compounds via three different post-polymerization modification chemistries — acetalization, thio-acetalization, and thiol-ene reaction. Acetal-functionalized polycarbonates were studied in depth to exploit their acid-labile acetal functionalities. Acetalization of the amphiphilic diblock copolymer of poly(ethylene glycol) methyl ether (mPEG) and PMVEC, mPEG113-b-PMVEC13, with the model hydroxyl compound 4- methylbenzyl alcohol resulted in a maximum of 42% acetal and 58% hydroxyl side chain groups. Nonetheless, theamphiphilicity of the block polymer allowed for its self-assembly in water toafford nanostructures, as characterized via dynamic lightscattering and transmission electron microscopy. The kinetics of acetal cleavagewithin the block polymer micelles were examined in acidic buffered solutions (pH4 and 5). In addition, mPEG-b-PMVEC and its hydrolyzed polymermPEG-b-PMHEC (i.e., after full cleavage ofacetals) exhibited minimal cytotoxicity to RAW 264.7 mouse macrophages,indicating that this polymer system represents a biologically non-hazardousmaterial with pH-responsive activity.