Toward Functionalization of Thermoresponsive Poly(N-vinyl-2-pyrrolidone)

A series of new monomers with different substituents at the 3-position of N-vinyl-2-pyrrolidone (NVP) were synthesized. The substituents include simple alkyl (methyl, ethyl, propyl, and isopropyl), ether (methoxy ethyl and ethoxy ethyl), and functional groups (e.g., aldehyde, epoxy, and acetylene). These monomers were (co)polymerized radically to produce a family of (co)polymers based on poly(N-vinyl-2-pyrrolidone) (PVP), and the copolymer compositions could be controlled through varying comonomer feed ratio. When the monomers are substituted with ethyl-, methyl-, or ether-containing alkyl chains, their homopolymers are soluble in cold water but display sensitive and reversible phase transition upon heating to a cloud point temperature (CP). Control over CP of homopolymers was achieved by changing the hydrophilicity of the substituents. CP could also be tuned by copolymerization of different monomers or adding NaCl to the polymer aqueous solution. The mechanism of the thermoresponsive properties was studied by temperature-dependent H-1 NMR and microcalorimetry. The results confirmed that the phase transitions of (co)polymers bearing ether substituents were less cooperative with lower phase transition enthalpy and less dehydration even at temperatures well above the CP, and the transition is predominately liquid to liquid. In addition, aldehyde, epoxy, and acetylene groups were introduced to the (co)polymer chains as reactive groups; model reactions of these groups with other molecules were very efficient and simple. Thus, these polymers can subsequently be modified to impart additional functionality to be used as thermoresponsive polymers for bioconjugation. Finally, these polymers are demonstrated to be at least as biocompatible as PVP.