Computational study on the relative acidity of acetic acid by the QM/MM method combined with the theory of energy representation

We have applied the quantum mechanical/molecular mechanical (QM/MM) method combined with the theory of energy representation (ER) to study the acidity of acetic acid in aqueous solution. We have focused our attention on the relative acidity Δ_pK_a, of the molecule with respect to water solvent to circumvent the ambiguity of the solvation free energies of the molecular species referred to as proton. The value of Δ_pK _a for the acetic acid has been computed as -11.5 when we adopt the free energy change in the gas phase obtained by the B3LYP functional, which is in excellent agreement with the experimental value of -11.0. It has been demonstrated that the QM/MM-ER approach recently developed gives an adequate description for the solvation free energies related to the acidity/basicity calculations of organic molecules.