Rigorous pKa Estimation of Amine Species Using Density-Functional Tight-Binding-Based Metadynamics Simulations

Predicting pK_a values for different types of amine species with high accuracy and efficiency is of critical importance for the design of high performance and economical solvents in carbon capture and storage with aqueous amine solutions. In this study, we demonstrate that density-functional tight-binding-based metadynamics simulations are a promising approach to calculate the free energy difference between the protonated and neutral states of amines in aqueous solution with inexpensive computational cost. The calculated pK_a values were in satisfactory agreement with the experimental values, the mean absolute deviation being only 0.09 pK_a units for 34 amines commonly used in CO₂ scrubbing. Such superior reproducibility and correlation compared to estimations by static quantum mechanical calculations highlight the significant effect of dynamical proton transfer processes in explicit solvent molecules for the improvement of the estimation accuracy.