The relative pKa values of methyl-substituted ammonia homologues have been calculated a priori using a combined ab initio/free energy perturbation approach. The dependence of the results on basis set and geometry employed is investigated, and a detailed comparison with simulation data from another source is made. In general it is found that while relative pK, values can be calculated with a fair degree of accuracy the reproduction of subtle trends, where hydration effects are of crucial importance, is a far greater problem.
King, P. M., Reynolds, C. A., & Richards, W. G. (1990). The theoretical calculation of basicities: an homologous amine series. Journal of Molecular Structure: THEOCHEM, 208(3-4), 205-221. https://doi.org/10.1016/0166-1280(90)80007-B