Synthesis of Functional Polycaprolactones via Passerini Multicomponent Polymerization of 6‑Oxohexanoic Acid and Isocyanides

We describe a straightforward strategy for a new family of functional polycaprolactones (PCL) via the Passerini multicomponent polymerization (P-MCP) of 6-oxohexanoic acid and various isocyanides. Room temperature polymerization of tert-butyl isocyanide (1), 2,6-dimethyl­phenyl isocyanide (2), mOEG4 isocyanide (3), 5-isocyanopent-1-ene (4), and 5-isocyanopent-1-yne (5) with 6-oxohexanoic acid in CH2Cl2 generated PCL analogues (P1–P5) with different pendent groups amide-linked to the ε-position of PCL backbone. Furthermore, copolymerization of a mixture of isocyanides 1 and 3 in different molar ratios with 6-oxohexanoic acid produced copolymers (P6–P9) with adjustable properties. To demonstrate the high versatility of this platform polymer, polymer P4 with pendent alkene group was further modified with glucose via the thiol–ene click reaction. The structures of these (co)­polymers were confirmed by 1H NMR, 13C NMR, and matrix-assisted laser desorption ionization mass spectroscopy. The thermal properties of these (co)­polymers were examined by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). All these polymers are amorphous with variable glass transition temperatures (T g) depending on the side groups. For the copolymers, the dependence of T gs on comonomer composition was well predicted by the Fox equation. Degradation of water-soluble polymer P3 in aqueous solutions was investigated by 1H NMR and SEC. It was revealed that P3 was stable in D2O or pD = 5.8 phosphate buffer (PB) up to 15 days, while it completely degraded in basic condition over a period of 6 h and in acidic condition over a period of 24 h. Interestingly, polymer P3 even degraded steadily in pD = 7.4 PB by a random hydrolysis mechanism. Two polymer samples were examined to be nontoxic. Thus, this novel class of PCL analogues can be easily engineered to tailor its material properties and degradation behavior and may have great potential as new degradable materials to meet biomedical applications.