Feasibility of enantiomeric separation of racemic compounds using a simple method: Theoretical investigation of anion ability to conglomerate crystal formation of ketamine salts

In the pharmaceutical industry, there is a special interest in the resolution of chiral compounds to obtain enantiopure drugs. Conglomerate mixture is of considerable interest, since it corresponds to the possibility of spontaneous resolution of the two enantiomers. The aim of this paper was to find the achiral anions causing the conglomerate formation of Ketamine salts. For this purpose, the effect of 7 anion (X) on the heterochiral structure of Ketamine enantiomers salts was studied by Material Studio software. The crystal structures of all systems were determined by quantum calculations of CASTEP module. The investigation of the crystal structures and their respective energy showed that Ketamine salts, formed by Fumaric acid and Succinic acid, crystalized as conglomerate, favoring preferential crystallization. The AIM results confirmed the more stability of conglomerate crystal in these cases while in the presence of other salting agents as Oxalic acid, Formic acid, Carbonic acid, Acetic acid and Hydrochloric acid, racemic crystal form was calculated as the more stable crystal. Using the Forcite module, the total energy of the crystalline systems, calculated as the sum of the energies of the bonded and non-bonded interactions, are in agreement with those predicted by CASTEP module and AIM calculations.