Enzymatic catalysis in the synthesis of new polymer architectures and materials

Over the last decade, progress in the research towards enzymatic ring-opening polymerization has lead to novel, biocatalytic, and cleaner processes for the synthesis of polymeric materials. So far, this research has predominantly been focused on how to utilize the enzyme’s selectivity to synthesize and modify polymers, which cannot easily be achieved via chemical routes. However, proper understanding of these processes has not been obtained yet. Additionally, already present polymers have been enzymatically synthesized for biomedical applications, without the use of a metal catalyst, e.g. poly(e-caprolactone). However, only little reports have been published on new materials, which were not readily accessible via traditional polymerization techniques. In this PhD research, the implementation of enzymes into polymer chemistry has been investigated, looking for an answer to the question: Can enzymes open new perspectives in polymer chemistry? Lipase was chosen as the enzyme for enzymatic ring-opening polymerization (e-ROP), as this is well-known in organic synthesis. The lipase that was used in this research is Candida antarctica Lipase B immobilized on an acrylic resin, which is commercially available under the name Novozym 435TM. The aim of this investigation is to (i) obtain insight into the critical parameters of e- ROP of lactones, and (ii) make new materials that are not (directly) accessible via chemical polymerization methods. In order to study the critical parameters of e-ROP of lactones, the present knowledge was investigated in more depth for e-caprolactone (e-CL) as monomer in the enzymatic synthesis of end-functionalized polymer using a functional initiator. It was found that only by optimizing reaction conditions such as temperature, presence of water, monomer concentration, and the type of initiator, well-defined polymeric structures could be obtained, thereby limiting the amount of polymeric side-products (i.e. polymer species that lack the specific end-group functionality). Moreover, the concentrations of end-functionalized polymer and the undesired side-products were quantified for the first time using Liquid Chromatography under Critical Conditions (LCCC). This technique has provided us new insights into the actual enzymatic process at different stages in the polymerization. Water appears to be the primary nucleophile during the initial stages of the reaction, even when all the reaction components are thoroughly dried. Depending on the type of functional initiator that is applied, this nucleophile is incorporated into the polymer, by both transesterification and initiation. Finally, cyclic polymer structures are formed during all stages of the reaction and their concentration depends strongly on the initial monomer concentration Subsequently, e-ROP was used in combination with controlled radical polymerization (atom transfer radical polymerization, ATRP) in order to investigate the compatibility of enzymes with other catalyst systems. All information that was previously obtained was used to synthesize a block copolymer (poly(CL-block-MMA)) by these two polymerization techniques. Ultimately, a cascade chemo-enzymatic polymerization was performed in which the two polymerization techniques were applied simultaneously from a bifunctional initiator to obtain a block copolymer. It was observed that enzymes are slowly deactivated in the presence of transition metals (i.e. copper- and nickel-based ATRP-catalysts), depending on the ligands used to coordinate these metals. Hence, cascade chemo-enzymatic synthesis is only feasible when the two catalysts are applied separately. In order to synthesize novel materials that are not (directly) accessible via chemical polymerization methods, a larger lactone (i.e. ¿-pentadecalactone, PDL) was polymerized using enzymatic ring-opening polymerization. Using chemical, metal-based catalysts, larger lactones cannot be polymerized to high molecular weight polyesters due to their low ringstrain, whereas enzymes have shown surprisingly high activity towards these monomers. The synthesis of this type of monomers opens a novel promising route to the production of biomedical materials. To test the mechanical properties of PPDL, the enzymatic synthesis was scaled up to obtain 30 g of polymer in one batch and optimized to obtain a polymer with a high molecular weight and a relatively narrow molecular weight distribution. The obtained PPDL was melt-spun into fibers, which after drawing show good properties for biomedical applications. In conclusion, it can be stated that enzymes do open new perspectives in polymer science. Careful analysis of the enzymatic process has revealed the critical parameters for proper enzymatic polymer synthesis. Enzymes can be used in combination with other catalysts and polymerization techniques to make polymer architectures that may not be directly available via chemical synthesis. Finally, a new range of monomers can be utilized specifically by enzymes to make novel, tailored biomedical materials.