A quick solvation energy estimator based on electronegativity equalization

ESE‐EE (Easy Solvation Estimation with Electronegativity equalization) is a quick method for estimation of solvation‐free energies ΔGº (solv), which uses a thoroughly fitted electronegativity equalization (EE) scheme to obtain atomic charges, which are further employed in a scaled noniterative COSMO‐like calculation to evaluate the electrostatic component of ΔGº (solv). Nonelectrostatic corrections including adjustable parameters are also added. For neutral solutes, ESE‐EE yields a mean absolute error (MAE) in ΔG (solv)° of 1.5 kcal/mol for aqueous solutions; 1.0 kcal/mol for nonaqueous polar protic solvents; 0.9 kcal/mol for polar aprotic solvents; and about 0.6 kcal/mol for nonpolar solvents. Since ESE‐EE only requires a molecular geometry as input for a ΔGº (solv) prediction, it can be utilized for a rapid screening of ΔGº (solv)for large neutral molecules. However, for ionic solutes, ESE‐EE yields larger errors (typically several kcal/mol) and is recommendable for preliminary estimations only. Upon a special refitting, ESE‐EE is able to yield partition coefficients with a good accuracy.