Cost-effective Poly( amino acids) Drieved from Ring-opening Polymerisation of 2,5-Diketopiperazine

Abstract

Poly(amino acids) (PAAs) are a pivotal class of polymers with significant applications in the biomedical field, notably in drug delivery systems and tissue engineering. While ring-opening polymerisation (ROP) of α-amino acid N-carboxy-anhydrides (NCAs) is a prevalent method for synthesising PAAs, its reliance on triphosgene makes it costly and environmentally unfriendly. Thus, this study aims to produce PAAs cost-effectively and eco-sensitively via ROP of 2,5-diketopiperazines (DKPs). An additional challenge is the production of PAA products that melt rather than decompose. Phe-DKP, Ala-DKP, and Sar-DKP were synthesised employing ethylene glycol and glycerol as solvents. To produce polyalanine (PAla), polyphenylalanine (PPhe), and poly(sarcosine-co-phenylalanine), the DKPs underwent ROP reactions across five to seven days. This process utilised anhydrous dimethylformamide (DMF) as the solvent, in conjunction with catalysts such as tin (II) octoate (Sn(Oct)2), aluminium chloride (AlCl3), and N,N-diisopropylethylamine (DIPEA). While limited solubility of Phe-DKP poses challenges, Ala-DKP and Sar-DKP display commendable solubility in anhydrous DMF at 130°C. The method not only emerges as economically and environmentally favourable but, with potential extrusion of the PAAs, also paves the way for crafting PAAs in diverse forms like films, fibres, or profiles.