Theoretical investigation of the solubility of some antiemetic drugs

Abstract

A theoretical study using density functional theory (DFT) is carried out to compare and explain the observed solubility of four antiemetic molecules, namely chlorpromazine, haloperidol, ondansetron and metoclopramide. The COSMO-RS (conductor-like screening model for real solvents) method is used to study the interaction between hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) of the antiemetic drugs, and their molecular interactions with water (dipole moments, interaction and solvation energies). In addition, the AIM (Atoms in Molecules) method is used to deeply study the hydrogen bonding interaction of the antiemetic drug which was found the most soluble in water, namely the metoclopramide. In fact, results show that atom O42 makes two H-bonds with two different water-oxygen atoms (BCP59 and BCP60). One of them, have another H-bond (BCP62) with the hydrogen H27. This study confirms that two of the three H-bonds with water are more stable than the intramolecular interaction between O9 and H27 (BCP1). These H-bonds are likely responsible of the highest solubility of metoclopramide.