Free energy calculations and solubility in water of organic molecules: a numerical relation through molecular dynamics

Solubility in water, free energy of solvation (ΔGsolv) and free energy of hydration (ΔGhyd) were determined for 86 organic liquids using Molecular Dynamics simulations in order to find out the relation among these properties. Both, correlation between ΔGhyd and solubility and correlation between ΔGsolv and solubility are not clearly defined. However, by defining Δs=ΔGsolv−ΔGhyd, it is found a numerical relation between Δs and solubility. This result was verified for pentane, ethanol and, hexanol of three different force fields (TraPPE-UA, CHARMM and, GROMOS). Also, it was studied the relation of these properties by increasing hydrophobicity in a functional group through the number of carbon atoms of the hydrocarbon chain. In this last case, the mentioned relation was also found.