Mechanistic limitations in the synthesis of polyesters by lipase‐catalyzed ring‐opening polymerization

Abstract Lipase‐catalyzed polymerization of caprolactone (CL) in toluene with methoxy‐poly(ethylene glycol) (MPEG) and water as initiators was characterized in detail for mechanistic insight. 1 H NMR analysis of polycaprolactone chains (PCL), dicaprolactone, degree of esterification of MPEG, and fractions of PCL chains initiated by MPEG and water were used to follow the reactions. The data were analyzed with the kinetic scheme involving formation of the acylenzyme and its consequent reaction with MPEG, water, or PCL to yield the MPEG‐ or water‐initiated PCL chains, or increase in PCL length. A limit for MPEG initiator esterification in lipase‐catalyzed CL polymerization was observed and was explained by preferential reaction of PCL propagation over MPEG esterification at long reaction times and low MPEG concentrations. Slower monomer conversion in concentrated monomer solutions was explained by decreased partitioning of PCL between the solvent and the enzyme. This effect resulted in inhibition of the lipase by the reaction product, PCL chains, and/or insufficient diffusion of monomer to the enzyme active site. High monomer/initiators ratio in these solutions did not yield longer polymer chains due to decreased monomer conversion and the corresponding decrease in product yields; lower yields were also observed for chain initiation by MPEG and water. A shift in the reaction rate‐limiting step from formation of acylenzyme in dilute CL solutions to its deacylation in concentrated CL solutions yielded higher PCL polydispersity due to increased initiation by water. Enhanced intramolecular cyclization was also observed. Endgroup composition of PCL chains was influenced by the concentration of monomer, ratio of initiators (MPEG and water), and reaction time, yielding PCL chains initiated exclusively by MPEG at “infinite reaction times.” © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 103–113, 2003.