Folding and formation of mesoglobules in dilute copolymer solutions

It is known that linear homopolymer chains can undergo a coil-to-globule-to-precipitation transition when the solvent quality gradually changes from good to poor. It is also known that the observation of the coil-to-globule transition without any interchain association is extremely difficult if not impossible. On the other hand, the folding of individual amphiphilic copolymer chains, such as protein chains, in an extremely dilute solution is much easier. As the copolymer concentration increases, inevitable interchain association accompanied by intrachain folding can result in a stable mesoglobular phase (the aggregation of a limited number of chains), existing between single-chain globules and macroscopic phase separation (precipitation). In this article, we mainly review what we have accomplished in the last ten years by starting with a brief discussion of the folding of linear poly(N-isopropylacrylamide) (PNIPAM) homopolymer chains in water. Our focus is the folding of different hydrophdically or hydrophobically modified PNIPAM copolymer chains in extremely dilute solutions as well as the formation of stable mesoglobules made of amphiphilic copolymer chains in dilute solutions. The discoveries of the molten globular state and the ordered- coil state between the random-coil and compacted globular states will be illustrated. The effects of both the comonomer composition and distribution on the folding of individual copolymer chains into some unique core-shell nanostructures as well as the formation of the mesoglobular phase are discussed. The double roles of hydrophobic interaction in the formation and stabilization of stable mesoglobules will be explained in terms of the viscoelastic effect.