Investigation of enantiomeric separation of tiletamine drug using computational chemistry methods

In this paper, the ability of organic reagents such as the succinate, oxalate, maleate, fumarate, adipate, glutarate, suberate, and pimelate anions in separation of different enantiomer form of tiletamine compound (R&S) is investigated using the density functional theory method (DFT). Our findings showed that the conglomerate crystal of tiletamine is formed in the presence of succinate, oxalate, fumarate, and maleate organic reagents. Moreover, the racemic mixture of tiletamine is formed in the presence of adipate, glutarate, suberate, and pimelate anions. According to the thermodynamic parameters of tiletamine-organic anion interactions, it is revealed that, in comparison to chloroform, internal thermal energy, enthalpy, and Gibbs free energy become more positive in the presence of ethanol and water solvents indicating the enfeeble effect of solvent polarity on enantiomer separation. Also, it should be noted that the existence of carbon chain lengths greater than three atoms in the organic anion is not suitable for enantiomeric separation. The natural bond orbital (NBO) and Atom In Molecules (AIM) results show that tiletamine nitrogen atom is the primary site of interaction with the oxalate, succinate, fumarate, and maleate anions.