Organocatalytic Ring-Opening Polymerization Toward Poly(γ-amide-ε-caprolactone)s with Tunable Lower Critical Solution Temperatures

γ-Amide-ε-caprolactones including 7-oxo-N-propyloxepane-4-carboxamide (NNCL), N-isopropyl-7-oxooxepane-4-carboxamide (NICL), N,N-diethyl-7-oxooxepane-4-carboxamide (DECL), and 5-(pyrrolidine-1-carbonyl)­oxepan-2-one (VPyCL) were initially designed and synthesized to achieve biodegradable and thermosensitive materials. Ring-opening polymerization (ROP) of these newly developed caprolactones was thoroughly investigated by both theoretical calculation and experimental verification. Density functional theory revealed that the ring-opening enthalpy of γ-amide-ε-caprolactones was more negative than that of γ-ester-ε-caprolactone (EMCL). Experimental results showed that ROP of NICL, DECL, and VPyCL catalyzed by 1,5,7-triazabicyclo[4.4.0]­dec-5-ene with benzyl alcohol (BnOH) as an initiator underwent in a living and controlled manner, while that of NNCL and EMCL did not. Computational calculation consistently proved that a variety of substitutions greatly affected the ROP process. PNICL, PDECL, and PVPyCL exhibited reversible lower critical solution temperature-type phase transitions tuned by manipulating the feed ratio and hydrophilicity of comonomers. Furthermore, poly­(γ-amide-ε-caprolactone)­s with excellent biodegradability and biocompatibility were demonstrated as an enzyme activity regulator, holding great promise for smart biomaterial application.