Biodegradable polyester copolymers: synthesis based on the Biginelli reaction, characterization, and evaluation of their application properties

Abstract

The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted end-group modifications on a variety of biodegradable polyesters, including poly(1,4-butylene adipate) (PBA), poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(p-dioxanone) (PPDO), based on the precursor polyethylene glycol (PEG). By combining two polymers through the Biginelli multi-component reaction, four new biodegradable polyester copolymers, namely DHPM-PBA, DHPM-PCL, DHPM-PLA, and DHPM-PPDO, were formed. These Biginelli reactions demonstrated exceptional completeness, validating the efficiency of the synthesis strategy. Although the introduction of various polyesters lead to different properties, such as crystallinity and cytotoxicity, the newly synthesized 3,4-dihydro-2(H)-pyrimidinone compounds (DHPMs) exhibit enhanced hydrophilicity and can self-assemble in water and N,N-dimethylformamide (DMF) solution to form micelles with a controllable size. Furthermore, DHPM-PPDO promotes cellular growth and has potential applications in wound healing and tissue engineering. In conclusion, this method demonstrates great universality and methodological significance and offers insights into the medical applications of polyethylene glycol.

Fig. 1. (a) PEG-based Biginelli reaction. (b) Mechanism of the Biginelli Reaction. (c) Schematic of synthesis of DHPMs products.

Fig. 2. (a) XRD curves, (b and c) DSC heating curves, and (d and e) DTG curves of PEG, PBA, PCL, PPDO, PLA, DHPM–PBA, DHPM–PCL, DHPM–PLA, and DHPM–PPDO. (f) SEM images of DHPM–PBA, DHPM–PCL, DHPM–PLA, and DHPM–PPDO.

Fig. 3. (I) TEM of micelles (a) DHPM–PBA, (b) DHPM–PCL, (c) DHPM–PLA, and (d) DHPM–PPDO. (II) Size regulation of micelles.

Fig. 4. (a) Water contact angles of PEG, PBA, PCL, PPDO, PLA, DHPM–PBA, DHPM–PCL, DHPM–PLA, and DHPM–PPDO. (b) Degradation rates of DHPM–PBA, DHPM–PCL, DHPM–PLA, and DHPM–PPDO. Cell viability of DHPM–PBA (c), DHPM–PCL (d), DHPM–PLA (e), and DHPM–PPDO (f).