Chemosynthetic P4HB: A Ten-Year Journey from a “Non-Polymerizable” Monomer to a High-Performance Biomaterial

ConspectusAliphatic polyesters consisting of hydrolytically and/or enzymatically degradable ester bonds in each repeating unit possess diverse thermomechanical properties and desired biodegradability and biocompatibility, thus, finding broad applications in biomedical fields. Among them, poly(4-hydroxybutyrate) (P4HB) is a biomaterial receiving particular attention, due to its proper thermal transition temperatures (Tg ∼ – 50 °C, Tm ∼ 60 °C) relative to the environment of living systems, excellent mechanical properties (high toughness and extensibility when molar mass is sufficiently high), and facile degradability in aqueous media where living systems function. The production of P4HB has long relied on biological fermentation, where it is stored in fermented cells and extracted at the end of the fermentation. However, the high production cost of the fermentation process, associated with its slow reaction kinetics and presently limited production volume, hinders broader implementations of P4HB. In addition, biological routes typically produce P4HB with poor control over the polymer molar mass and dispersity, and postfermentation treatment is employed to offer various molar mass P4HB formulations. Considering that chemical catalysis generally offers faster reaction kinetics, more rapid catalyst tuning, a higher degree of control, and better scalability, it would be desirable to develop a chemocatalytic route to access P4HB more rapidly, at scale, and on-demand for tailorable chain lengths and architectures. In this context, developing the effective and efficient chemocatalytic synthesis of P4HB through ring-opening polymerization (ROP) of γ-butyrolactone (γBL), which is bioderived and available at scale, is of great interest and significance.The ROP of γBL was first attempted in 1932 and followed subsequently using various conditions, but those attempts only led to the formation of oligomers, due to the negligible ring strain of the five-membered lactone ring that renders γBL (commonly referred to as) “nonpolymerizable”. Ten years ago, we first isolated the semicrystalline, chemosynthetic P4HB from the ROP of γBL and then in 2016 reported the first effective chemocatalytic synthesis of P4HB with useful molar mass of Mn ∼ 30 kDa, through investigating the thermodynamics of the polymerization to identify appropriate conditions for the effective ROP, exploring the catalysts to enhance the ROP rate and selectivity, and optimizing the reaction/process conditions to continuously perturb the thermodynamic equilibrium for achieving high monomer conversions far exceeding the thermodynamic limit. Since then, the field of chemosynthetic P4HB has witnessed significant advances contributed by many research groups worldwide. In this Account, we will describe the recent advances made in the catalyzed ROP of γBL, which have culminated with the achievement previously thought not possible: high-molar-mass P4HB with an absolute molar mass of Mn up to 171 kDa and toughness up to 267 MJ m–3 while exhibiting complete chemical recyclability for closed-loop chemical circularity. The fundamental aspects of thermodynamic manipulations, kinetic considerations, and reaction/process conditions that enabled this breakthrough are critically analyzed, and copolymerization approaches and monomer redesign for P4HB derivatives with vastly tunable properties and universal chemical recyclability due to the γBL core are also discussed.