Prediction of partition coefficients and infinite dilution activity coefficients of 1-ethylpropylamine and 3-methyl-1-pentanol using force field methods

The octanol–water partition coefficients (Ko/w) and infinite-dilution activity coefficients (γ∞) of 1-ethylpropylamine and 3-methyl-1-pentanol were predicted based on free energy calculations. The multi-configuration thermodynamic integration (TI) method was applied with molecular dynamics simulations to calculate free energy changes. With optimized simulation options and force field parameters the calculated free energy changes were highly precise (uncertainties <0.52 kJ/mol) and accurate (deviations <2.7 kJ/mol from the experimental data). Although this accuracy level is comparable with the best reported in the literature, it was still too low to yield accurate predictions of Ko/w and γ∞ coefficients. Nevertheless, the predictions were close to those obtained using general QSPR methods.