Since the pioneering study of da Silva and Svendsen, numerous studies have used a similar thermodynamic-cycle-based approach to investigate the deprotonation reaction pK a value, whereas similar studies for the carbamate reversion equilibrium constant pK c are extremely limited. While some studies show reasonable accuracy (a mean absolute deviation from experiment below 0.5 pK unit), they usually require a particular combination of gasphase quantum chemical theory/basis set and solvation model that is often different from the original quantum chemical method used for the solvation model development, questioning the transferability of such approaches to different classes of compounds. More rigorous direct ab initio simulation of the free-energy profile of the dissociation reaction taking place in the condensed phase has been shown to be a promising route for pK a estimation. However, apart from being extremely computationally demanding, such simulations may require advanced sampling techniques to escape from local free energy minima, inhibiting their wide-spread use for rapid solvent screening. In a recent paper, we developed a molecular-based framework for reactive absorption in CO 2 -amine-water systems without any amine-specific experimental data or experimental proton hydration free energy data only using the pK c and the equilibrium constant of the following isoelectric reaction (one with the same total numbers of positive and negative charges on the reactant and product side), which is the reaction combination R3-R1-R2 of the above reaction set: