Thermodaynamic Origin of Cononsolvency

Cononsolvency is a phenomenon for which the solubility of a polymer or protein decreases or even vanishes in the mixture of good solvents. Although it is widely used in physicochemical, green chemical and pharmaceutical industry, it’s origin is still under debates for decades. A few theoretical explanations were proposed based on experimental results on conformation variation of polymer chains on the length scale of tens of nanometer. Here, by using combined neutron total scattering and all-atom molecular dynamic simulation, we present a universal thermodynamic explanation of cononsolveny, based on strong solvent-solvent attraction. The mixed solvent structure at molecular level in a few angstroms is successfully connected to the polymer conformation with dimension around several nm. Our study opens up many directions to explore all-atom structure in macromolecular solution and the origin of its solubility.