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.

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.

Polyphosphazene polyacids show potential as immunostimulating compounds and materials for microencapsulation. Their synthesis requires multistep chemical transition from a hydrolytically unstable macromolecular precursor, poly(dichlorophosphazene), to a water-soluble polyelectrolyte. Insufficient synthetic control in these reactions can lead to molecular weight variations and formation of macromolecules with "structural defects" resulting in significant variations in polymer performance. Simple and reproducible "one pot-one solvent" method is reported for the preparation of polyphosphazene polyacids-poly[di(carboxylatophenoxy)phosphazene] and its copolymers. Molecular weight characteristics and polymer compositions were studied as a function of reaction parameters. Macromolecular byproducts, incompletely substituted polymers containing hydroxyl groups and partially deprotected polymers containing propyl ester functionalities, were synthesized and characterized. It was demonstrated, that the presence of such groups can affect polymer characteristics, such as hydrolytic degradation profiles, immunostimulating activity, and microsphere forming properties. In vivo studies showed that the immunostimulating activity of polyphosphazene polyacids correlates with the content of acid functionalities in the polymer.

This work was directed at extending the use of lipase-catalyzed ring-opening polymerizations to cyclic carbonate monomers. Of the seven lipases screened for bulk trimethylene carbonate (TMC) polymerization (70 °C, 120 h), Novozym-435 from Candida antarctica gave almost quantitative monomer conversion (97%) and poly(TMC) with a Mn ) 15 000 (Mw/Mn ) 2.2) with no apparent decarboxylation during propagation. The lipases from Pseudomonas species (AK and PS-30) and porcine pancreas (PPL) also exhibited high monomer conversions (>80%, 120 h) but gave lower molecular weight polymers with broad polydispersity. Analyses by 1 H-NMR spectroscopy suggested that poly(TMC) prepared by Novozym-435-catalyzed polymerization had terminal -CH2OH functionalities at both chain ends. A monotonic increase in monomer conversion with time and the rapid increase in Mn as a function of monomer conversion for Novozym-435-catalyzed TMC bulk polymerization at 70 °C suggest that the polymerization has chain-type propagation kinetics. An increase in conversion above 66% did not substantially change Mn. The percent conversion was larger when the reaction temperature was increased from 45 to 55 °C. Further increase in the reaction temperature from 55 to 85 °C did not give higher percent conversion values. The molecular weight decreased substantially as the reaction temperature was increased from 55 to 85 °C (Mn from 24 400 to 5 900). The highest poly(TMC) molecular weight (Mn ) 24 400) was obtained by conducting the polymerization at 55 °C. Monomer conversion and molecular weight as a function of the percent reaction water content (w/w) were investigated. Increasing the water content resulted in enhanced polymerization rates and decreased molecular weights. Separation of the oligomeric products from polymerizations of TMC in dried dioxane and toluene catalyzed by porcine pancreatic lipase led to the isolation of di-and triadducts of trimethylene carbonate. Based on the symmetrical structure of these products and the end-group structure of high molecular weight chains, a mechanism for chain initiation and propagation for lipase-catalyzed TMC polymerization was proposed.

The lipase-catalyzed stereoelective ring-opening polymerization of racemic α-methyl-β-propiolactone (MPL) was investigated. Using the lipase PS-30 from Pseudomonas fluorescens, a direct route to optically active (S)-enriched poly(α-methyl-β-propiolactone), PMPL, was demonstrated. From a comparative study of different organic media, polymerizations conducted in toluene and heptane proceeded more rapidly than those carried out in dioxane. The enantiomeric ratios E in toluene, heptane, and dioxane were 4.1 ± 0.2, 0.9, and 2.0, respectively. Thus, from the point of view of reaction rates and enantioselectivity, toluene was found to be the preferred solvent. PMPL products prepared in toluene by PS-30 catalysis had M n values from 2600 to 2900 g/mol and [α]25 D +12.2° to +19.0° (c 0.9 g/dL, CHCl3). Analysis of the polymer chain end structure by 1H and 13C NMR showed that these products have hydroxyl and carboxylic acid termini. Based on the analysis of chain stereosequence distributions by 13C NMR, it was concluded that stereoselectivity during propagation results from catalyst enantiomorphic-site control. Investigation of the thermal behavior of PMPL (75% (S)) by DSC showed that melting occurs over a broad region from ∼25 to 100 °C where the total ΔH f is 12.7 cal/g.