The polymerization of e-caprolactone, (e-CL) using porcine pancreatic lipase (PPL) as the catalyst was studied. Polymerization reactions (4 days, 65 °C) of e-CL at ~10% (w/v) concentrations in dioxane, toluene, and heptane using butanol as an initiating species (monomer/butanol ratio = 14.7) gave poly(e-caprolactone) (PCL) with Mn values (by GPC) of 313, 753, and 1600, respectively. Monomer conversion to PCL for these polymerizations was 33, 55, and 100%, respectively. Mn measurements of PCL products by NMR end group analyses were slightly lower (by a factor of -0.9) than the values obtained by GPC. Polymerizations conducted in heptane at 37, 45, 55, and 65 °C showed the highest extent of monomer conversion at 65 °C. Therefore, subsequent studies were conducted at 65 °C in heptane. For a polymerization carried out with a 15/1 monomer/butanol ratio and ~0.29 mmol of water, ~70 and ~100% of the monomer had been converted to PCL by reaction times of 24 and 96 h, respectively. Polymer molecular weight increased slowly with conversion, suggesting that this is a chain polymerization with rapid initiation and slow propagation. Increases in the e-CL/butanol ratio from 15/1 up to where no butanol was added showed only a modest increase in product molecular weight from 1600 to 2700. This was explained by the fact that the water present in polymerizations was active in chain initiation. Variation in the monomer/butanol ratio at constant water concentration resulted in PCL chains with 0-0.65 mol fraction of butyl ester and 0.33-0.86 mol fraction of carboxylic acid chain end groups (by NMR analyses). The presence of water concentrations in polymerization reactions above that which is strongly enzyme bound is believed to be an important factor which limited the formation of PCL chains of significantly higher molecular weight.

Lipase-catalyzed ring-opening bulk polymerizations of ω-pentadecalactone (PDL) were investigated. Screening of selected commercial lipases as catalysts for PDL polymerization at 80 °C was carried out. The results of this work showed that polymerizations catalyzed by lipases PS-30, AK, Lipozyme-IM and Novozym-435 gave % PDL conversions ranging from 80 to 100% for 24 h reactions (M n = 15 000−34 400). Lipase PS-30 both physically immobilized onto Celite-521 (I-PS-30) and in the crude powder or nonimmobilized form (NI-PS-30) was selected for further study. Comparison of % conversion vs time for bulk PDL polymerizations at 70 °C catalyzed by NI- and I-PS-30 showed that for short reaction times, the immobilized catalyst gave % conversions that were more than 10 times greater. In fact, the % monomer conversion to poly(PDL) was nearly quantitative (>98%) for 8 h polymerizations catalyzed by I-PS-30. Furthermore, for reactions conducted at 70 °C with careful removal of water, substantially greater poly(PDL) molecular weights resulted by using I-PS-30 instead of NI-PS-30 as the catalyst. Increasing the % conversion above ∼40% for PDL polymerizations at 70 °C resulted in little or no change in PDL M n. This is consistent with chain polymerizations where the rate of propagation is much faster than initiation. The general trends observed by variation of the I-PS-30 catalyzed bulk PDL polymerization temperature were the following:  (i) increased % conversion and M n by increasing the reaction temperature from 60 to 70 °C and from 60 to 80 °C, respectively, (ii) similar polymerization rates between 70 and 90 °C, and (iii) a decrease in % monomer conversion and M n as the reaction temperature was increased from 90 to 110 °C. It was found that water was an important factor that controls not only the rate of monomer conversion but also the polymer molecular weight. From an increase in the water content in reactions, enhanced polymerization rates were achieved while the molecular weight of poly(PDL) decreased. At low reaction water levels (0.20% w/w water), the I-PS-30 catalyzed polymerization of PDL at 70 °C gave poly(PDL) with M n and M w/M n of 62 000 and 1.9, respectively. Thus far, this is the highest molecular weight polyester prepared by an enzyme-catalyzed polymerization reaction.

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.

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The one-pot biocatalytic synthesis of novel amphiphilic products consisting of an ethyl glucopyranoside (EGP) headgroup and a hydrophobic chain is described. The porcine pancreatic lipase (PPL) catalyzed ring-opening polymerization of -caprolactone ( -CL) by the multifunctional initiator EGP was carried out at 70 °C in bulk. Products of variable oligo( -CL) chain length (M n ) 450, 2200) were formed by variation of the -CL/EGP ratio. Extension of this approach using Candida antarctica lipase (Novozym-435) and EGP as the initiator for trimethylene carbonate (TMC) ring-opening polymerization also resulted in the formation of an EGP-oligo(TMC) conjugate (M n ) 7200). Structural analysis by 1 H, 13 C, and COSY ( 13 C-13 C) NMR experiments showed that the reaction was highly regiospecific; i.e., the oligo( -CL)/oligo(TMC) chains formed were attached by an ester/carbonate link exclusively to the primary hydroxyl moiety of EGP.