Scalable synthesis and derivation of functional polyesters bearing ene and epoxide side chains

Abstract

Functional polyester chemistry is well suited to improve delivery of biomacromolecular drugs because it enables tuning of degradation profiles and inclusion of key functional groups (e.g. cationic charges for nucleic acid binding). However, current approaches to introduce functionality suffer from inadequate scalability and modularity. We have developed a scalable library of functional polyesters based on the polymerization of trimethylolpropane allyl ether (TPAE) with diacid chlorides (poly(TPAE-co-AC)s). The reactive side chains can be easily modified with various functional thiols (e.g. alkyl-, amino-, and PEG-) and amines to generate a diverse set of materials, thereby tuning the chemistry for potential opportunities in drug delivery. The polymerization occurs readily under mild conditions at room temperature with M_w for poly(TPAE-co-suberoyl chloride) exceeding 42 000 g mol⁻¹. In addition, poly(TPAE-co-adipoyl chloride) was polymerized on a 100+ gram scale in 71% final isolated yield. Due to the structural similarity to established non-functional polyesters such as PLGA, these new materials may find broad application as functional polyesters for gene delivery, tissue engineering, and other nanotechnology applications.