ABSTRACT
Absolute pKa calculations rely on four items: (1) a thermodynamic cycle that relates the gas phase to the solution phase; (2) knowledge of relevant experimental values; (3) accurate gas-phase calculations; and (4) accurate solvation calculations. Once an appropriate thermodynamic cycle is devised, then state-of-the-art quantum chemical calculations are used with the cycle to estimate pKa values [15]. These estimates can be quite accurate for small molecules, but are of course limited to systems small enough where highly accurate quantum mechanical values can be calculated.
