and the carbamate reversion reaction R2, both of which are isocoulombic (with the same number of like-charged species on the reactant and the product side). Use of an isocoulombic reaction has been shown to provide a better estimate of the temperature trend for its equilibrium constant. Furthermore, such reactions have the advantage that for activity coefficient models based on the Debye-Huckel approximation (e.g., the Davies model), the ionic contributions to the reaction free energy change cancel. We test this approach for the equilibrium constants (pK a and pK c ) for a much larger set of 77 primary, secondary and tertiary amines, Our approach combines ideal-gas calculations with explicit solvent MD simulations in TIP3P water using the fast AM1-BCC partial charge assignment method for the amine molecules and their protonated and carbamate forms, which we have previously shown to be superior to the RESP-based charges for pK a prediction used in our previous work. To enable the use of the isocoulombic reaction R1, we develop a new GAFF-compatible force field for H 3 O + to be used in conjunction with TIP3P water by matching the wellknown experimental MEA deprotonation equilibrium constant at 298.15 K. This enables the H 3 O + FF to be used to calculate the pK a of reaction R1 as a function of temperature, both for MEA and all other alkanolamines. We further validate the H 3 O + FF by comparing its indirect prediction of proton hydration free energy with the well-established literature value at 298.15 K, 24 and also use it to calculate the intrinsic proton solvation free energy as a function of temperature. 2 Thermodynamic Background 2.1 Molecular-based framework for the calculation of pK a and pK c