Polydepsipeptides (PDPs) are strictly alternating copolymers of α-hydroxy acids and α-amino acids produced via the ring-opening polymerization (ROP) of morpholino-2,5-dione derivatives (MDs). They have been used as promising biomaterials for their combined high thermal stability and good mechanical properties of polyamides as well as the inherent degradability of polyesters. ROP of MDs is usually carried out at high temperatures with metal catalysts or enzymes, with less control over the polymer molecular weights and dispersities. In this work, we developed a simple and efficient synthetic strategy of a new platform MD via the Passerini-type reaction between an isocyano derivative of the amino acid and an aldehyde, followed by intramolecular esterification. Nine new MDs were synthesized by using this method, and the organobase-catalyzed ROP of these MDs was investigated. When the ROPs of these MDs were catalyzed by either triazabicyclo[4.4.0]dec-5-ene (TBD) or diazabicyclo[5.4.0]undec-7-ene (DBU) in the presence of benzyl alcohol as an initiator, the polymerizations were uncontrolled with the formation of both linear PDPs and cyclic PDPs. By using binary catalytic systems of 1-(3,5-bis(trifluoromethyl)-phenyl-3-cyclohexyl-2-thiourea) (TU) with DBU or TBD ([TU]/[TBD] or [DBU] > 3), the polymerizations became well-controlled, allowing the synthesis of PDPs with controlled molecular weights, low dispersities, as well as block copolymers. Furthermore, cyclic PDPs were obtained when the ROP of these MDs was catalyzed with TBD in the absence of both TU and an initiator. Finally, we used two methods to recover the monomer precursors or pure MD monomers: the TBD-catalyzed alcoholysis of PDPs was very fast and generated the monomer precursors quantitatively, while the acid-catalyzed depolymerization of PDPs led to pure and quantitative monomer recovery.

The selective Passerini reactions of 4-formylbenzoic acid and 4-isocyanobenzoic acid with aliphatic isocyanides and aldehydes were utilized to synthesize sequence-defined uniform macromolecules. Our strategy does not involve any protecting groups or reactive group transformation steps and allows direct and consecutive propagation of sequence in each step. Introduction of diverse side groups by using different aliphatic components provided a range of sequence-defined uniform macromolecules in high yield and gram scale. The strategy also allows further Passerini self-coupling or cross-coupling of the formed sequences with other small molecules, affording polymers with up to 5098.3 Da and 20 side groups. Thus, this strategy will show promise for more efficient synthesis of new sequence-defined macromolecules.

We describe a straightforward synthetic strategy for a new family of functional poly­(ester–amide)­s (PEAs) with tertiary ester linkages via the Passerini multicomponent polymerization (Passerini-MCP) of a diacid (A2), 1,6-diisocyanohexane (B2), and four kinds of electron-deficient ketones. First, Passerini three-component reactions (Passerni-3CR) of hexanoic acid and tert-butyl isocyanide with nine kinds of ketones were investigated to evaluate the reactivities of these ketones toward Passerni-3CR. Four electron-deficient ketones, 1,1,1-trifluoroacetone (1), 1,1,1-trifluoro­acetophenone (2), ethyl pyruvate (3), and 2,3-butanedione (4), were found to be excellent oxo-compounds for this Passerini-3CR. Then, the Passerini-MCP of A2 and B2 with 1, 2, 3, and 4 in CH2Cl2 was performed to generate polymers P1–P4 with tertiary ester linkages and different electron-withdrawing substituents. Polymer P5 was also prepared by the Passerini-MCP of A2 and B2 with phenyl­acetaldehyde (5) for comparison. Size exclusion chromatography (SEC) verified the high molecular weights (M n up to 30.6 kDa) of these polymers. The structures of these polymers were confirmed by 1H NMR, 13C NMR, 19F NMR, and matrix-assisted laser desorption ionization mass spectroscopy. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) revealed that P1–P4 are less stable than polymer P5, and they are amorphous with variable glass transition temperatures (T g) depending on the side groups. Hydrolytic degradation of P1, P4, and P5 in a mixture of acetonitrile and phosphate buffer (different pH) was investigated, and at the same pH, the degradation follows the order of P4 > P1 > P5. The static water contact angles of thin films formed by these polymers decreased from 96° (P1) to 78° (P2), 50° (P3), and finally to 32° (P4). Tensile properties of polymer P3 and P4 were characterized by dynamic mechanical analysis (DMA). P4 displayed a high tensile stress of 25 MPa with the elongation up to 200%.