Journal of the American Chemical Society, Vol.117, No.22, 6057-6063, 1995
Solvation Free-Energies of Amides and Amines - Disagreement Between Free-Energy Calculations and Experiment
We present molecular dynamics/free energy calculations on the molecules acetamide, N-methylacetamide, N,N-dimethylacetamide, ammonia, methylamine, dimethylamine, and trimethylamine. Unlike the experimental data, which suggest a very non-additive solvation free energy (N-methylacetamide and methylamine having the most negative free energy of solvation), the calculations all find that the free energy of solvation monotonically increases as a function of methyl addition. The disagreement with experiment is surprising, given the very good agreement (within 0.5 kcal/mol) with experiment for calculation of the solvation free energy of methane, ethane, propane, water, methanol, and dimethyl ether.
Keywords:MOLECULAR-DYNAMICS;PERTURBATION CALCULATIONS;POTENTIAL FUNCTIONS;LIQUID WATER;GAS-PHASE;HYDRATION;SIMULATION;CHARGES;BOND;PARAMETERS