Theoretical Investigation of Inclusion Complex between Omeprazole Enantiomers and Carboxymethyl-β-Cyclodextrin

Abstract

Host-guest inclusion complexes between R/S-Omeprazole (R/S-OME) enantiomers with Carboxymethyl-β-Cyclodextrin (CM-β-CD) is proposed to predicts the separation of its enantiomers that considering the interaction energy and inclusion geometry. The inclusion complex structures were built into two orientations i.e. 1: 1 and 2: 1 as the ratio of host to guest. All structures were optimized by two methods i.e. molecular mechanic docking and quantum semi empiric PM3. Based on the value of binding energy obtained from the computational modelling, it was found that inclusion complex of S-Omeprazole with Carboxymethyl-β-Cyclodextrin (S-OME/CM-β-CD) is more stable than the inclusion complex of R-Omeprazole with Carboxymethyl-β-Cyclodextrin (R-OME/CM-β-CD). Moreover, R/S-Omeprazole can form stable inclusion complexes with Carboxymethyl-β-Cyclodextrin by the ratio of host: guest equal to 2: 1. Other thermodynamic parameter values, i.e. Enthalpy (ΔH), Entropy (ΔS), and Gibbs free energy (ΔG) show that the inclusion complex of S-OME/CM-β-CD is more exothermic, more spontaneous, and preferably formed when compared to inclusion complex of R-OME/CM-β-CD. In addition, the formation of the R/S-OME inclusion complex with Carboxymethyl-β-Cyclodextrin (CM-β-CD) is an enthalpy driven process based on these values.