Recent Developments in Metal-Catalyzed Ring-Opening Polymerization of Lactides and Glycolides: Preparation of Polylactides, Polyglycolide, and Poly(lactide-co-glycolide)

Abstract

A good synergy of a catalytic system’s components, such as ancillary ligands and leaving groups at the active site of a catalyst, is of fundamental importance in the ring-opening polymerization (ROP) of lactides and lactones. This article surveys recent advances in the metal-promoted ROP of lactide and glycolide for the preparation of poly(lactide) (PLA), poly(glycolide) (PGA), and their copolymer poly(lactide-co-glycolide) (PLGA). First, there is a general discussion on mechanisms, the undesirable effects of side reactions on the rate of polymerization, and how the first generation of ROP catalysts such as SnOct2 [tin(II) 2-ethylhexanoate, also known as tin(II) octoate] work as efficient initiators. Then, the study focuses on the ROP capability of monomeric and multinuclear complexes of Li, Ca, Mg, Zn, Al, and Ti metals for the efficient preparation of PLA. Special emphasis is given to the factors controlling polymer molecular weight, molecular weight distribution, and the suppression of transesterification side reactions and epimerization of monomers. Surpassing the pure model nature of many structurally well-defined catalytic systems such as bis(phenoxide)-Li, bis(phenoxide)-Mg, trispyrazolylborate-Mg/Zn, and β-diketiiminate-Mg/Zn, the applicability and performance of N,O-donor Schiff base Mg/Zn systems in the production of PLAs are highlighted. The emerging “structure-polymerization” activity is also addressed. Special attention is given to Ca, Mg, and Zn initiators which, due to their biocompatibility, are considered the safest to be used in the preparation of PLAs for biomedical purposes. Likewise, the polymerization activity of the metal initiators is evaluated on the basis of the Lewis acidic properties of the central metal. Alternatives like trivalent lanthanide systems with ancillary ligands such as bis(amidinate), β-ketoiminate, bis(phenolate), and Schiff bases are considered. Some recently investigated coordination complexes of Cu, Ni, Ag, and Au metals used in the solvent-free melt polymerization of lactide are discussed in terms of structure–activity relationships. The substantial role of the ligand geometry on the stereocontrol of the rac-lactide polymerization is addressed to finally summarize the key components essential for obtaining PLAs of desired microstructure from rac- and meso-lactides. The development of glycolide ROP catalysts based on Sn, Zn, Sm, and Bi is addressed and their effectiveness in producing copolyesters of lactide and glycolide such as PLGA assessed.