Water/Cosolvent Attraction Induced Phase Separation: A Molecular Picture of Cononsolvency

Cononsolvency is a phenomenon for which the solubility of a macromolecule decreases or even vanishes in the mixture of two good solvents. Although it has been widely applied in physicochemical, green chemical and pharmaceutical industry, its origin is still under active debate. Here, by using combined neutron total scattering, deuterium-labelling and all-atom molecular dynamic simulations, we demonstrated that it is the strong water/cosolvent attraction that leads to the cononsolvency. The combined approach presented here has opened a new route for investigating the most probable all-atom structure in macromolecular solutions and the thermodynamic origin of solubilities.