Catalyst Improved Stereoselectivity and Regioselectivity Control to Access Completely Alternating Poly(lactic-co-glycolic acid) with Enhanced Properties

Xuanhua Guo; Hassan Ahmed; Guangqiang Xu; Qinggang Wang

doi:10.1002/anie.202417075

Catalyst Improved Stereoselectivity and Regioselectivity Control to Access Completely Alternating Poly(lactic-co-glycolic acid) with Enhanced Properties

Angew Chem Int Ed Engl. 2024 Dec 24:e202417075. doi: 10.1002/anie.202417075. Online ahead of print.

Authors

Xuanhua Guo¹, Hassan Ahmed², Guangqiang Xu¹, Qinggang Wang³

Affiliations

¹ Qingdao Institute of BioEnergy and Bioprocess Technology Chinese Academy of Sciences, Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy, No.189 Songling Road, Laoshan District, Qingdao, 266101, CHINA.
² Qingdao Institute of BioEnergy and Bioprocess Technology Chinese Academy of Sciences, Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy, CHINA.
³ Qingdao Institute of BioEnergy and Bioprocess Technology Chinese Academy of Sciences, Bio-based Materials, Songling Road 189., 266101, Qingdao, CHINA.

PMID: 39719855
DOI: 10.1002/anie.202417075

Abstract

The poly(lactic-co-glycolic acid) (PLGA) with completely alternating sequence has attracted growing attention as an ideal candidate in controlled drug delivery. However, the approach to completely alternating PLGA remains a challenge. Herein, we report the successful synthesis of completely alternating PLGA via highly regioselective and stereoselective ring-opening polymerization. The chiral (BisSalen)Al catalyst promoted a robust polymerization of enantiopure 3-methyl glycolide (MeG) with highly glycolic site selectivity, affording alternating PLGA with regioselectivity up to more than 99%. Impressively, the completely alternating PLGA exhibited a well-defined melting temperature Tm of 143.1 °C. Moreover, a stereocomplex between PLLGA and PDLGA was also formed with the improved Tm of 211.8 °C. The In vitro degradation and drug release experiments revealed the linear degradation and controlled drug release behavior of completely alternating PLGA, which can be used as an ideal carrier for mild long-acting drug delivery. Meanwhile, the reason of the high regioselectivity was investigated through the control experiments and DFT calculation. This highly regioselective (BisSalen)Al catalyst opens a door to providing completely alternating polymers.

Keywords: biodegradable polyester, poly(lactic-co-glycolic acid), completely alternating sequence, regioselective polymerization, dual-ligand strategy.