Quantum mechanics calculations on the diastereomeric salts of cyclic phosphoric acids with ephedrine

Using three different density functional packages. DMol3, VASP, and SIESTA, we have calculated the relaxed structures and relative energies of the diastereomers of cyclic phosphoric acid and its chlorine derivative with ephedrine. The structures predicted by the three codes are in very good agreement with experiment. Also in accordance with experiment, very small energy differences (<3 kcal/mol) are found between diastereomers. However all the three packages fail to correctly reproduce the stability order of all diastereomers. This failure is probably related to the inability of the currently available approximations for the exchange-correlation energy functional to reproduce dispersive long-range interactions (i.e. van der Waals). In spite of the large unit cell, the relative stability of the different structures is quite sensitive to the k-space sampling. On the one hand, VASP and SIESTA codes predict the correct stability order when only Γ point is used for the k-space integration. A better k-space sampling however, destroys the agreement between theory and experiment, increasing the energy of the experimentally most stable chlorine-containing diastoreomer. On the other hand, DMol3, with which only Γ point calculations have been performed; predicts the stability order of one pair of diastereomers correctly, but the stability order of a third polymorph is predicted wrongly. An experimentally unknown chlorine-free analogue of the most stable chlorine-containing diastereomer, was calculated to be the least stable.