Enzyme-Catalyzed Polymerizations of ε-Caprolactone:  Effects of Initiator on Product Structure, Propagation Kinetics, and Mechanism

Abstract

Studies were undertaken to gain mechanistic information on lactone ring-opening polymerization reactions using porcine pancreatic lipase (PPL) as the catalyst and ε-caprolactone (ε-CL) as the monomer. Polymerizations were carried out at low water levels (0.13 mmol) and supplemented with either butanol or butylamine. Rates of monomer conversion, product molecular weight, total chain number, and chain end structure were determined by 1H NMR. In the presence of water alone, a maximum M n of 7600 g/mol was obtained at 85% conversion, which decreased to 4200 g/mol as the reaction continued to 98% conversion. Reactions with butanol and butylamine at 100% conversion gave polymers with M n values of 1900 and 1200 g/mol, respectively. For these three polymerizations, the total number of polymer chains increased with conversion due to a simultaneous increase in carboxylic acid chain ends. Within 4 h (∼26% monomer conversion), butylamine was completely consumed but only 37% of butanol reacted. Reactions with butylamine occurred predominantly by an enzyme-mediated route to form N-butyl-6-hydroxyhexanamide. This step was rapid relative to subsequent chain growth. In addition, the living or immortal nature of the polymerizations was assessed from plots of log{[M]0/[M] t } versus time and M n versus conversion. These results indicate that termination and chain transfer did not occur, and we described the system as providing “controlled” polymerizations. Furthermore, an expression for the rate of propagation was derived from the experimental data which is consistent with that derived from the proposed enzyme-catalyzed polymerization mechanism. The absence of termination in conjunction with the relationship between molecular weight and the total concentration of multiple initiators suggests that ε-CL polymerization by PPL catalysis shares many features of immortal polymerizations.

Study on the enzymatic polymerization mechanism of lactone and the strategy for improving the degree of polymerization

“…In particular, the variation of water content during polymerization and its relationship to DP have been neglected, as well as the effect of reaction media, although investigators did use various organic solvents as polymerization media. 25,27,29,30 Our investigation focuses on the influence of water content and reaction media on polymerization.…”

Polymers in the Pharmaceutical Applications - Natural and Bioactive Initiators and Catalysts in the Synthesis of Biodegradable and Bioresorbable Polyesters and Polycarbonates

“…Lipases could also catalyze ROP of cyclic monomers, with different ring sizes as well as monomers containing substituents in the ring: -methyl--propiolactone (1), -butyrolactone (2), -caprolactone (3), -methyl-valerolactone (4), 1,4-dioxan-2-one (5), -caprolactone (6), -ethyl--caprolactone (7), -heptanolactone (8), -decalactone (9), -dodecalactone (10) Coŕdova et al, 1999;Divakar, 2004;Dong, 1998Dong, , 1999Gorke et al, 2007;Henderson et al, 1996;Kobayashi, 2001aKobayashi, , 2001bKobayashi, , 2009MacDonald et al, 1995;Marcilla et al, 2006;Matsumoto et al, 1999;Mei et al, 2003;Namekawa et al, 1999;Rokicki, 2000;Sivalingam & Madras, 2004;Van Der Mee et al, 2006). Lipases can accommodate a wide variety of synthetic substrates and still be able to show stereo-and regio-selectivity.…”

“…The yield of the obtained polymers varied from 10 to 100%. The preferred lipase system generally used is a physically immobilized form of Candida Antarctica, commercially available as Novozyme-435 (Barrera-Rivera et al, 2009;Coŕdova et al, 1999;Divakar, 2004;Dong, 1998Dong, , 1999Gorke et al, 2007;Henderson et al, 1996;Kobayashi, 2001aKobayashi, , 2001bKobayashi, , 2009MacDonald et al, 1995;Marcilla et al, 2006;Matsumoto et al, 1999;Mei et al, 2003;Namekawa et al, 1999;Sivalingam & Madras, 2004;Van Der Mee et al, 2006).…”

Candida antarctica Lipase B as Catalyst for Cyclic Esters Synthesis, Their Polymerization and Degradation of Aliphatic Polyesters

“…Biodegradable polyesters, obtained in this clean process, are used in biomedical applications as scaffolds and in drug delivery systems. Enzymatic ring-opening polymerization (eROP) of lactones can be conducted in the presence of different lipases derived from microorganisms such as: bacteria (Pseudomonas fluorescens [5], Burkholderia cepacia [6,7]), yeast species (Yarrowia lipolytica [8]), lipases of animal origin (porcine pancreas [9]), as well as thermophilic lipase/esterase family enzyme from the archaeon Archaeoglobus fulgidus [10,11], nevertheless during last decades the most intensively studied for this purpose was lipase B from yeast Candida antarctica (CALB). CALB exhibits high polymerization catalytic activity of lactones containing from 4 to 17 membered rings [12], but in the case of lactide, only low molar mass oligomers were achieved [13].…”