Synthesis of functional polyesters by lipase-catalyzed ring-opening polymerization

Polymerization reactions catalyzed by enzymes produce polymers that are biodegradable and relatively pure due to the reaction specificity and absence of toxic metal catalysts and initiators during synthesis. Lipase-catalyzed polymerization of lactones is one example of these reactions and offers a promising approach to the synthesis of polyesters. No by-products such as alcohols are produced, and functionalized oligomers and polymers can be prepared. In the current work two approaches to controlled polyester synthesis using lipases are addressed: terminal functionalization by the initiator, and use of lactones that yield functional pendant groups after ring-opening polymerization.; Compounds with one or more nucleophilic (usually hydroxyl) groups have been found to initiate enzyme-catalyzed lactone polymerization. We are interested in reactions that can lead to control over di- and tri-block formation in lactone ring-opening reactions in the presence of symmetrical bifunctional initiators such as poly(ethylene glycol)s (PEGS). Regioselectively initiated diblock copolymers would be useful in biomaterials and drug delivery. Currently chemical protection/deprotection steps are employed to generate PEG-polymer diblocks for these applications. Polymerization of caprolactone and pentadecalactone initiated by PEGs of different lengths and catalyzed by immobilized Candida antarctica lipase (Novozyne 435) were studied. The reaction mixtures consisted of both regioselectively and non-regioselectively initiated polyesters. In order to interpret the results polymerization reactions were also conducted with monofunctional PEG. The reaction mechanism was found to be a potential origin for regioselectivity (formation of PEG-polyester diblocks only). This mechanistic study also clarified earlier contradictions in the literature on the rate-limiting step in the enzyme-catalyzed lactone ring-opening polymerization and explained reaction behavior in hydrophobic solvents.; Lipase-catalyzed polymerization of lactones yielding pendant carboxyl groups on the polyester backbone was performed with alkylmalolactonates as monomers with a wide range of side chains and functional groups. This family of polyesters is important in tailored synthesis of degradable polymers for biomedical applications. Mechanistic features of malolactonate polymerization in the presence of Candida rugosa lipase was gained for new options for the tailored synthesis of poly(alkyl malates).; In summary, the results illustrate potential paths forward for highly controlled synthesis of well-defined polyesters by using an enzymatic approach. The mechanistic features identified with these reactions also highlight the limitations of the approach.