The theoretical calculation of basicities: an homologous amine series

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.