Comment on “On the positional and orientational order of water and methanol around indole: a study on the microscopic origin of solubility” Phys. Chem. Chem. Phys., 2016, 18, 23006

Abstract

In a recent article, Phys. Chem. Chem. Phys., 2016, 18, 23006, MD simulations have been used to clarify why indole is much more soluble in methanol than in water. Structural data indicate that water and methanol make very similar interactions with the indole molecule and do not provide clues to rationalize the origin of the solubility difference. In the present comment, I have shown that the relevant quantity is the magnitude of the reversible work of cavity creation. The latter magnitude proves to be markedly larger in water than in methanol, clarifying why most non-ionic solutes, with the exception of molecules able to form multiple H-bonds, such as urea, are more soluble in methanol.