  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.
