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How the solvent modulates the weak inter-particle interactions in solution and affects macromolecule solubility is not yet understood. Well-established thermodynamic relationships link second virial coefficient and preferential solute binding parameter. We present the meaning of these thermodynamic parameters and the way to measure them. When a solvation shell has a composition different from the bulk solvent, a negative contribution is found in the second virial coefficient corresponding to an effective attraction between the macromolecules in solution. A quantitative evaluation using simple models of solvated particles in solution suggests that solvation could induce, at high or low concentration of a small molecule solute, attractive inter-particle interactions corresponding to favorable crystallization conditions.
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