Aliphatic polyester is an important polyester material with good biocompatibility and degradability, which can be synthesized through ring-opening alternating copolymerization (ROAC) of epoxides and anhydrides. Herein, density functional theory (DFT) is used to explore the mechanism of ROAC of epoxides (propylene oxide (PO), styrene oxide (SO), epichlorohydrin (ECH), and cyclohexane oxide (CHO)) and phthalic anhydride (PA) catalyzed by bis(triphenylphosphine) ammonium chloride (PPNCl) and ureas. It was found that the ring-opening polymerization (ROP) of epoxides is the rate-controlling step, and the benzyl alcohol (BnOH) as the initiator has little effect on the polymerization activity, which was consistent with previous experimental results. Calculated comparisons of the ROAC activity of CHO/PA catalyzed by four different ureas indicate that as the Lewis acidity of the urea increased, the energy barriers of the copolymerization increased and the activity decreased. The main reason was that the strong hydrogen-bonding interactions stabilized the key intermediate of the rate-controlling step and inhibited subsequent monomer insertion. Based on this, a series of new ureas with higher catalytic activity were designed by introducing electron-donating substituents. In SO polymerization, increasing the Lewis acidity of urea can improve the SO regioselectivity. In addition, the monomer ECH with CH₂Cl shows higher activity of ROAC than PO and SO, which could be ascribed to the fact that the strong electron-withdrawing Cl atom stabilizes the transition state in the rate-controlling step and reduces the reaction energy barrier.

Aliphatic polyesters, widely used in biomedicine due to their biocompatibility and biodegradability, are typically synthesized via the ring-opening polymerization (ROP) of cyclic esters. Although traditional metal catalysts are highly active, their biological toxicity limits their applications. Organocatalysts, particularly natural organic molecules, offer safer alternatives. We explored the ROP mechanisms of cyclic esters (L-Lactide (L-LA), ε-caprolactone (ε-CL), and δ-valerolactone (δ-VL)) catalyzed by phosphonium carboxybetaines (PCBs, (PhR)₃P⁺(CH₂)₂COO⁻, R = H(PCB), F(PCB-F) and OMe(PCB-OMe)) through density functional theory (DFT) computations. The DFT results revealed that the ROP of cyclic esters follows a bifunctional–cooperative activation mechanism, wherein the phosphonium moiety (Ph₃P⁺(CH₂)₂) activates the monomer via an extensive hydrogen-bonding interaction network, and the carboxylate (COO⁻) serves as a proton acceptor to enhance the nucleophilicity of the initiator phenylpropanol (PPA). In contrast, unsubstituted PCB exhibited the lowest energy barrier, being consistent with the highest catalytic activity among PCB derivatives observed experimentally. Moreover, a series of novel PCB derivatives (Ph₃P⁺(CH₂)_nCOO⁻, n = 3–6 (PCB1-PCB4)) were designed by regulating the carbon spacer length, and their catalytic performances were computationally tested. The designed catalyst PCB2 (Ph₃P⁺(CH₂)₄COO⁻) exhibited higher activity for the ROP of L-LA, attributed to providing sufficient flexibility to minimize deformation while improving proton-accepting capability. Similarly, PCB2 also demonstrated superior catalytic activity for δ-VL and the more challenging ε-CL monomer. This work not only clarifies the intrinsic catalytic nature of these zwitterionic organocatalysts, but also provides an effective strategy for the rational design of high-performance, metal-free catalysts for the synthesis of sustainable polyesters.