ARTICLE pubs.acs.org/Biomac
Lipase-Catalyzed Copolymerization of Dialkyl Carbonate with 1,4-Butanediol and ω-Pentadecalactone: Synthesis of Poly(ω-pentadecalactone-co-butylene-co-carbonate) Zhaozhong Jiang* Biomedical Engineering Department, Yale University, 55 Prospect Street, New Haven, Connecticut 06511, United States
bS Supporting Information ABSTRACT: Candida antarctica lipase B (CALB) was successfully used to promote synthesis of aliphatic poly(carbonate-coester) copolymers from dialkyl carbonate, diol, and lactone monomers. The polymerization reactions were carried out in two stages: first-stage oligomerization under low vacuum, followed by second-stage polymerization under high vacuum. Therefore, copolymerization of ω-pentadecalactone (PDL), diethyl carbonate (DEC), and 1,4-butanediol (BD) yielded PDL-DECBD copolymers with a Mw of whole product (nonfractionated) up to 33 000 and Mw/Mn between 1.2 and 2.3. Desirable reaction temperature for the copolymerization was found to be ∼80 °C. The copolymer compositions, in the range from 10 to 80 mol % PDL unit content versus total (PDL þ carbonate) units, were effectively controlled by adjusting the monomer feed ratio. Reprecipitation in chloroform/methanol mixture allowed isolation of the purified copolymers in up to 92% yield. 1H and 13C NMR analyses, including statistical analysis on repeat unit sequence distribution, were used to determine the polymer microstructures. The synthesized PDL-DEC-BD copolymers possessed near random structures with all possible combinations of PDL, carbonate, and butylene units via either ester or carbonate linkages in the polymer chains and are more appropriately named as poly(PDL-cobutylene-co-carbonate).
’ INTRODUCTION Aliphatic poly(carbonate-co-ester) copolymers are a group of important biomaterials known to be biodegradable.1 Commercial, medical-grade poly(carbonate-co-esters) include poly(glycolide-cotrimethylene carbonate) (Maxon) and poly(glycolide-co-trimethylene carbonate-co-p-dioxanone) (Biosyn). Such poly(carbonate-coesters) are preferred materials versus absorbable polyesters (e.g., poly(glycolide) (PGA) and poly(lactide-co-glycolide) (PLGA)) for constructing orthopedic fixation devices to fix tissue to bones. Clinical studies showed that upon degradation of PGA and PLGA, the formed byproducts glycolic acid and lactic acid are erosive to bones, and use of PGA or PLGA screws for fixing tissue to bones inhibited the bone growth and healing.2,3 The presence of carbonate units in the poly(carbonate-co-esters) alleviates the acidity problems caused by their degradation products because alkylene carbonate units undergo hydrolytic degradation to generate only neutral byproducts CO2 and aliphatic diol. Various chemical processes have been employed for preparation of poly(carbonate-co-ester) copolymers. For example, poly(butylene carbonate-co-butylene succinate) (poly(BC-co-BS)) was synthesized from either polycondensation of dimethyl succinate with 1,4-butanediol and diphenyl carbonate or chain extension reaction of poly(butylene succinate) diol with diphenyl carbonate using zinc and zirconium catalysts.4,5 Poly(BC-co-BS) copolymers with
