Candida polyester synthesis

In polyester synthesis via ring-opening polymerizations, metal catalysts are often used. For medical applications of polyesters, however, there has been concern about harmful effects of the metallic residues. Enzymatic synthesis of a metal-free polyester was demonstrated by the polymerization of l,4-dioxan-2-one using Candida antarctica lipase (lipase CA). Under appropriate reaction conditions, the high molecular weight polymer (molecular weight = 4.1 x 10" ) was obtained. 

Candida antarctica lipase B chemically immobilized on epoxy-activated micro-and nanobeads Catalysts for polyester synthesis. Biomacromolecules, 9 (2), 463-471. 

Although there are notable exceptions as given below, the most common lipase-catalyst used for polyester synthesis is Candida antarctica lipase B (CALB) (please refer to Chapter 14 for more information on the structure and reaction mechanisms of CALB). The immobilized CALB catalyst that has been primarily used is Novozym 435, manufactured by Novozymes (Bagsvaerd, Denmark). Novozym 435 consists of CALB physically adsorbed within the macroporous resin Lewatit VPOC 1600 (poly[methyl methacrylate-co-butyl methacrylate], supplied by Bayer) (please refer to Chapter 3 for more information on Novozym 435). 

In recent years, the enzymatic synthesis of biodegradable polyesters was focused on the polycondensation method (22,23). Among the very few successful example of enzymatic ring-opening polymerization for polyesters synthesis, Novozyme-435 (immobilized lipase B from Candida antartica) has been proved an effective catalyst for polycaprolactone (PCL) synthesis in toluene (24). Considering the low cost and high recyclablity of IPPL, we also... 

Effects of Porous Polyacrylic Resin Parameters on Candida antarctica Lipase B Adsorption, Distribution, and Polyester Synthesis Activity... 

Polyacrylic resins were employed to study how immobilization resin particle size influences Candida antarctica Lipase B (CALB) loading, fraction of active sites, and catalytic properties for polyester synthesis. CALB adsorbed more rapidly on smaller beads. Saturation occurred in less than 30 seconds and 48 h for beads with diameters 35 and 560-710 pm, respectively. Infrared microspectroscopy showed that CALB forms protein loading fronts for resins with particle sizes 560-710 and 120 pm while CALB appears evenly distributed throughout 35 pm resins. The fraction of active CALB molecules adsorbed onto resins not influenced by particle size was less than 50 %. At about 5% w/w CALB loading, decrease in the immobilization support diameter from 560-710 to 120,75 and 35 pm increased conversion of s-CL to polyester (20 to 36, 42 and 61%, respectively, at 80 min). Similar trends were observed for condensation polymerizations of 1,8-octanediol and adipic acid. 

Hiroshi et al. reported [46] a high-performance immobilized lipase catalyst for polyester synthesis. A porous polypropylene was found to be a good support for immobilization of Candida antarctica lipase (enzyme). The immobilized lipase on polypropylene efficiently catalyzes ring opening polymerization of 15-pentadecanolide, polycondensation of divinyl sebacate, and 1,8-octanediol. 

Chen, B., J. Hu, E. M. Miller, W. Xie, M. Cal, and R. A. Gross. 2008. Candida Antarctica Lipase B Chemically Immobilized on Epoxy-Activated Micro- and Nanobeads Catalysts for Polyester Synthesis. Biomacromolecules 9 (2) 463-471. 

In case of PLA and other polyester synthesis, lipase catalyst has been nsed and found to be efficient. Lipase is usually an enzyme that catalyzes the hydrotysis of fatly acid esters in living systems and sometimes, can also be used as catalyst for esterification and transesterifications. Lipase enzyme can be derived from Candida cylindracea. Pseudomonas cepacia, Pseudomonas fluorescens, and Porcine pancreas, which are powdery and commercially available crude enzymes (Albertsson and Varma, 2003). 

Those lipases that have been reported for the polyester synthesis are of mammalian (porcine pancreatic lipase, PPL) or fungal (Candida antartica, CA Candida rugosa, CR Candida cylindracea, CC Aspergillus niger, AN PeniciUium roureforti, PR Rhizopus delemar, RD Rhizomucor miehei, RM) or bacterial origin (Pseudomonas cepacia, PC Pseudomonas Jlourescens, PF Pseudomonas species lipase, PS) and so on. 

Other authors have described the lipase-catalyzed chemoselective acylation of alcohols in the presence of phenolic moities [14], the protease-catalyzed acylation of the 17-amino moiety of an estradiol derivative [15], the chemoselectivity in the aminolysis reaction of methyl acrylate (amide formation vs the favored Michael addition) catalyzed by Candida antarctica lipase (Novozym 435) [16], and the lipase preference for the O-esterification in the presence of thiol moieties, as, for instance, in 2-mercaptoethanol and dithiotreitol [17]. This last finding was recently exploited for the synthesis of thiol end-functionalized polyesters by enzymatic polymerization of e-caprolactone initiated by 2-mercaptoethanol (Figure 6.2)... 

Lipase-catalyzed synthesis of PBS is a recently developed method, which is fulfilled at milder conditions without remnant metal salt. In 2006, Azim et al. (2006) reported Candida antarctica lipase B catalyzed synthesis of PBS from the monophasic reaction mixtures of diethyl succinate and 1,4-butanediol. The reaction temperature played an important role in determining the molecular weight of PBS. After polymerization for 24 h in diphenyl ether, PBS with of 2,000,4,000, 8,000, and 7,000 was produced at 60, 70, 80, and 90°C, respectively. The low molecular weight was due to precipitation after polymerization for 5-10 h, limiting the growth of the polyester chain length. Increasing the polymerization temperature from 80 to 95°C can result in the maintenance of a monophasic reaction mixture after 21 h, which led to production of PBS with of 38,000 and polydispersity index of 1.39. 

Enzymatic synthesis of a methacrylamide-type polyester macromonomer was reported (80,81). In the polymerization of 12-hydroxydodecanoic acid in the presence of 11-methacryloylaminoundecanoic acid using lipase CC or Candida antarctica lipase (lipase CA) as catalyst, the polymerizable group was quantitatively incorporated into terminal of the poljmier chain. 

Enzymatic polymerization has emerged in the last few decades as a field of considerable interest and commercial promises. It proceeds with high regio-, enantio-, and chemos-electivity under relatively mild conditions. So far, enzymes have been used to synthesize polyesters, polysaccharides, polycarbonates, polyphenols, polyanilines, vinyl polymers, and poly(amino acid)s. Namely, the lipase B of Candida antarctica (Cal-B, a serine hydrolase) immobilized on polyacrylic resin (Novozyme 435) has proven to be a very versatile catalyst in terms of reaction conditions and acceptance of various substrates. For example, this enzyme has been successfully used to synthesize polyesters. ° However, little has been reported so far on the synthesis of polyamides catalyzed by enzymes. " ... 

Synthesis of linear silicone aliphatic polyesters by the condensation polymerization of l,3-bis(3-carboxypropyl)tetra-methyldisiloxane with alkanediols (1,4-butanediol, 1,6-hex-anediol and 1,8-octanediol) using an immobilized lipase B from Candida antarctica (Novozym-435) as a catalyst, as shown in Scheme 2.2, has been reported [21]. These reactions were performed in the bulk (without the use of solvent) in the temperature range 50-90°C under reduced pressure (50-300 mmHg, vacuum gauge). 

Based on the specific reaction that they catalyze, enzymes have been classified into six groups, three of which have been reported to catalyze or induce polymerization in vitro, namely oxidoreductases, transferases and hydrolases. The latter class includes hpases, the natural role of which is the hydrolysis of fatty acid esters at the cell s water-Upid interface. In organic media, hpases can efficiently catalyze ester bond formation, and so have been used extensively in investigations of the in vitro synthesis of polyester by polycondensation or ring-opening polymerization (ROP), without the need for any cocatalyst. One enzyme that deserves special attention when discussing enzymatic ROP is Candida antarctica Lipase B (CALB). 

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