Mechanistic Studies on the Lipase-Catalyzed Ring-Opening Polymerization of Lactones

Abstract

KEY WORDSEnzymatic Polymerization I Ring-Opening Polymerization 1 Michaelis-Menten Kinetics I Lactone I Macrolide I Recently, polyester syntheses through enzymatic catalysis with various monomer combinations have been extensively investigated. 1 By utilizing specific enzymatic catalysis, enantioselective 2 · 3 and regioselective 4 polymerizations have been developed. To obtain polymers of higher molecular weight in high yields, activated diesters having 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, or vinyl leaving groups have been often used as monomers for the enzymatic polycondensation. 5 · 6Enzymatic syntheses of aliphatic polyesters have also been achieved by ring-opening polymerization and copolymerization of lactones. 7 -16 Until now, small-( 4-membered) and medium-size lactones (6-and 7-membered) as well as macrolides (12-, 13-, and 16-membered lactones) were polymerized by lipase catalysts. In particular, these macrolides having much lower anionic polymerizability than e-caprolactone (e-CL) exhibited unusually high reactivity through lipase catalysis. 11 · 12 · 15 The lipase-catalyzed polymerization of the macrolides proceeded much faster than that of e-CL, which is the reversed tendency of chemical reactions such as an alkaline hydrolysis 17 and anionic ring-opening polymerizations.18 To quantitatively evaluate the lipase-catalyzed polymerizability of these lactones, we made MichaelisMenten kinetics of the polymerization. 19 This study is the first example to shed light on the mechanistic aspect via kinetics on the enzymatic ring-opening polymerization of lactones. EXPERIMENTAL Materialse-CL, 12-dodecanolide (DDL), and iso-propyl ether were stored over freshly activated type 4 molecular sieves. Pseudomonas fluorescens lipase (lipase PF) was donated by Amano Pharmaceutical Co. and used without further purification. Kinetic StudyTo a dried 50 mL flask was added e-CL or DDL, 1-octanol (0.039 g, 0.30 mmol), lipase PF (200 mg), and iso-propyl ether (10 mL). The flask was kept at 60°C under gentle stirring. An aliquot (10--20 JlL) of the reaction mixture was removed every 1 h and subjected to gas chromatographic (GC) analysis for determination t To whom correspondence should be addressed.of the monomer conversion. MeasurementsGC analysis was carried out using a Shimadzu GC-14B apparatus equipped with an FID detector and a TC-5 column (GL Sciences). 1 H NMR spectra were recorded on a 400MHz Bruker DPX-400 spectrometer. Water content was measured using a Mitsubishi Kasei V A-06 Karl Fischer titrator. RESULTS AND DISCUSSIONThe enzymatic polymerization of lactones was carried out using lipase PF in iso-propyl ether at 60°C. Monomers used in this study were e-caprolactone (7-membered, e-CL) and 12-dodecanolide (13-membered, DDL). Lipase PF has high catalytic activity for these monomers. 7 · 12 After 48 h, the chloroform-soluble part of the reaction mixture from DDL monomer was analyzed by 1 H NMR spectroscopy. The product was found to be a mixture of the unreacted monomer and the corresponding oligomer. 10 On the b...

Polyesters

“…This intermediate then reacts with the terminal hydroxyl group of a n-mer chain to produce an (n + 1)-mer. 325,355,358,359 Enzymatic lactone polymerization follows a conventional Michaelis-Menten enzymatic kinetics 353 and presents a "controlled" character, without termination and chain transfer, 355 although more or less controlled factors, such as water content of the enzyme, may affect polymerization rate and the nature of endgroups. 360 …”

Enzyme-catalyzed ring-opening polymerization of 3(S)-isopropylmorpholine-2,5-dione

“…Enzymatic syntheses of aliphatic polyesters have been studied extensively [11][12][13][14][15][16][17][18][19][20][21][22] . Medium-size lactones (6-and 7-membered) as well as macrocyclic lactones (12-, 13-, and 16-membered) are polymerized with lipases as catalysts yielding the corresponding polyesters [17][18][19][20][21] .…”

“…Macrolides with small ring strain, which hence show low anionic polymerizability, were found to be polymerized much faster with lipases than CL 20,21) . This is due to a favored transition state of the macrolide to open the ring 22) . Although the enzymatic ring-opening polymerization of lactones and cyclic carbonates was studied in detail by many researchers, the enzymatic polymerization of morpholine-2,5-diones to the best of our knowledge has not been reported so far.…”

Lipase-Catalyzed Ring-Opening Polymerization of Lactones in the Presence of Aliphatic Polyesters to Ester Copolymers

“…[23,24] This is probably due to the stronger recognition of the lipases toward the macrolide. The polymerization of 1 was carried out using pseudomonas fluorescens lipase (lipase PF) as catalyst in the presence of poly(ecaprolactone) (2) with a number-average molecular weight of 1.9 6 10 4 at 45 or 60 8C in anhydrous diisopropyl ether (Scheme 1).…”

“…The tendency that enzymatic reactivity is lower for 1 a than for 1 b in the present polymerization is also observed in the homopolymerization catalyzed by the same enzyme. [24,25,31] The copolymer structure was confirmed by 1 H and 13 C NMR spectroscopy. Except for the polymerization of 1 a at 45 8C (entry 1), the unit ratio determined by 1 H NMR was fairly close to the feed ratio.…”