Investigation of Lipase-Catalyzed Ring-Opening Polymerizations of Lactones with Various Ring Sizes:  Kinetic Evaluation

Abstract

Lipase-catalyzed ring-opening polymerizations of lactones with various ring sizes (6-to 13-and the 16-membered ring) employing Novozym 435 demonstrate fascinating differences in their polymerization rates. These differences cannot be related to variations in physical properties such as the dipole moment of the lactones only. For example, 10-decanolactone, 11-undecanolactone, and 12-dodecanolactone show dipole moments of around 1.9 D, but the initial rate constant of their Novozym 435-catalyzed polymerization was found to be 0.10, 0.38, and 4.91 h -1 , respectively. The Michaelis-Menten constants K M and V max were measured for all lactones, and this revealed that the K M was more or less independent of the ring size, suggesting similar affinities of the lipase for all lactones, while no obvious trend could be discerned for V max . However, conformational strain and transannular interactions present in medium ring lactones (ring size 8-12) affect the reactivity of these lactones in lipase catalysis in a similar way as was previously described for the alkaline hydrolysis of lactones, rationalizing the low reactivity of the 10-12-membered rings and the high reactivity of the 8-membered ring. To our surprise, there is a large discrepancy in lipase-catalyzed ring-opening polymerizations compared to the alkaline hydrolysis reactions with respect to the relative reactivity of lactones possessing a cisoid conformation of the ester bond: while the ratio in rates between δ-valerolactone and 12-dodecanolactone in a alkaline hydrolysis is 9400, the ratio in rates using Novozym 435-catalyzed polymerization is only 3. In fact, in the latter case lactones possessing a cisoid conformation are less reactive than large ring lactones possessing a transoid conformation. This mechanistic study also furnished polyesters with an increasing number of methylenes in their repeat unit. The polyesters can be readily prepared in reasonable molecular weights (>10 000 g/mol). Preliminary thermal characterization of the polyesters shows, as expected, that the melting temperature and the melting enthalpy increase with an increasing number of methylenes in the repeat unit.

Enzyme‐Catalyzed Ring‐Opening Polymerization of Unsubstituted β‐Lactam

“…Enzymes have been used so far to synthesize polyesters, polysaccharides, polycarbonates, polyphenols, polyanilines, vinyl polymers, and poly(amino acid)s. [1,2] The lipase B of Candida antarctica immobilized on polyacrylic resin (Novozyme 435) has proven to be a very versatile catalyst in terms of reaction conditions and the acceptance of various substrates, e.g., this enzyme has been used successfully to synthesize polyesters from linear [3] and cyclic [4][5][6][7] starting materials. Little, however, has been reported on synthesizing polyamides catalyzed by enzymes.…”

Incorporation of Primary Amines into a Polyester Chain by a Combination of Chemical and Lipase‐Catalyzed ε‐Caprolactone Ring‐Opening Processes

“…However, the nucleophilicity of the C-7 amino group allowed 2 to be acylated in the presence of a suitable reactive ester, even in the absence of the enzyme. We reasoned that the cyclic e-CL, due to its ring strain, [16] could be assimilated to an activated acyl donor when suffering the attack of a primary amino group, like that present in 2. In this way a new compound (2a) carrying a terminal, more accessible primary OH could be formed in situ.…”

Polymers in the Pharmaceutical Applications - Natural and Bioactive Initiators and Catalysts in the Synthesis of Biodegradable and Bioresorbable Polyesters and Polycarbonates

“…Lipases could also catalyze ROP of cyclic monomers, with different ring sizes as well as monomers containing substituents in the ring: -methyl--propiolactone (1), -butyrolactone (2), -caprolactone (3), -methyl-valerolactone (4), 1,4-dioxan-2-one (5), -caprolactone (6), -ethyl--caprolactone (7), -heptanolactone (8), -decalactone (9), -dodecalactone (10) Coŕdova et al, 1999;Divakar, 2004;Dong, 1998Dong, , 1999Gorke et al, 2007;Henderson et al, 1996;Kobayashi, 2001aKobayashi, , 2001bKobayashi, , 2009MacDonald et al, 1995;Marcilla et al, 2006;Matsumoto et al, 1999;Mei et al, 2003;Namekawa et al, 1999;Rokicki, 2000;Sivalingam & Madras, 2004;Van Der Mee et al, 2006). Lipases can accommodate a wide variety of synthetic substrates and still be able to show stereo-and regio-selectivity.…”

“…The yield of the obtained polymers varied from 10 to 100%. The preferred lipase system generally used is a physically immobilized form of Candida Antarctica, commercially available as Novozyme-435 (Barrera-Rivera et al, 2009;Coŕdova et al, 1999;Divakar, 2004;Dong, 1998Dong, , 1999Gorke et al, 2007;Henderson et al, 1996;Kobayashi, 2001aKobayashi, , 2001bKobayashi, , 2009MacDonald et al, 1995;Marcilla et al, 2006;Matsumoto et al, 1999;Mei et al, 2003;Namekawa et al, 1999;Sivalingam & Madras, 2004;Van Der Mee et al, 2006).…”