Lipase-catalyzed polymerization, cyclic monomers

Lipase-Catalyzed Polymerization of Dicarboxylic Acids or Their Derivatives. Enzymatic synthesis has been achieved via various combinations of dicarboxylic acid derivatives and glycols. As to the diacid monomer, dicarboxylic acids, activated and nonactivated esters, cyclic acid anhydrides, and polyanhydrides were enzymatically reacted with glycols under mild reaction conditions. 

Polycarbonates have attracted attention in recent years because of their potential use in biomedical applications based on their biodegradability, biocompatibility, low toxicity and good mechanical properties [67]. These polymers can be prepared by the ROP of cyclic carbonate monomers by anionic, cationic, and coordination catalysts. However, lipase-catalyzed polymerization seems to be a feasible alternative to prepare polycarbonates as chemical methods often suffer from partial elimination of carbon dioxide (resulting in ether linkages), require extremely pure monomers and anhydrous conditions. 

The polymerization of dimethyl maleate and 1,6-hexanediol proceeded using lipase CA catalyst in toluene to give the polymer exhibiting exclusively cis structure [55]. During the polymerization, cyclic oligomers were formed. The cycles were semi-crystalline, whereas the linear polymer was amorphous. In the lipase CA-catalyzed copolymerization of dimethyl maleate and dimethyl fumarate with 1,6-hexanediol, the content of the cyclization was found to depend mainly on the configuration and concentration of the monomers [56]. 

Lipase-Catalyzed Ring-Opening Polymerization of Cyclic Monomers... 

Polyester syntheses have been achieved by enzymatic ring-opening polymerization of lactide and lactones with various ring-sizes. Here, we focus not only on these cyclic esters but also other cyclic monomers for lipase-catalyzed ringopening polymerizations. Figure 8 summarizes cyclic monomers for providing polyesters via lipase catalysis. 

Besides cyclic esters and carbonates, six-membered cyclic depsipeptides and a five-membered cyclic phosphate were subjected to lipase-catalyzed ring-opening polymerizations, yielding poly (ester amide)s190 and polyphosphate,191 respectively. High temperatures (100—130 °C) were required for the polymerization of the former monomers. 

There is, of course, an equilibrium between the monomers and polymer in the lipase-catalyzed polycondensation of dialkyl esters and glycols. In the lipase CC- or MM-catalyzed polymerization of dimethyl succinate and 1,6-hexanediol in toluene, adsorption of methanol by molecular sieves or elimination of methanol by nitrogen bubbling shifted the thermodynamic equilibrium (101). When dicar-boxy lie acid dialkyl esters and a , >-alkylene glycols were used as monomers, cyclic oligomers were formed from any monomer combinations examined (102). The yield of the cyclics depended on the monomer structure, initial concentration of the monomers, and reaction temperature. The ring-chain equilibrium was observed and the molar distribution of the cyclic species obeyed the Jacobson-Stockmayer equation. 

In this chapter we provide a brief description of Upase-catalyzed ROP, where we use the word enzyme to refer only to lipase. First, we will discuss the specific characteristics of enzymatic ROP, indudtng the mechanistic and kinetic aspects of the reaction. We will then introduce the most important classes of cyclic monomers in enzymatic ROP, after which we will review the use of enzymatic ROP in the synthesis of more complex polymer architectures. For further information, the reader is referred to recent reviews on enzymatic polymerization [3-7]. 

Conventional ring-opening polymerization of cyclic anhydrides, carbonates, lactones, and lactides require extremely pure monomers and anhydrous conditions as well as metallic catalysts, which must be completely removed before use, particularly for medical applications. To avoid these difficult restrictions, an enzymatic polymerization may be one of the more feasible methods to obtain the polyesters. This method was first reported by two independent groups (Kobayashi [152] and Gutman [153]) who showed that lipases, enzymes capable of catalyzing the hydrolysis of fatty acid esters, can polymerize various medium-sized lactones. 

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