Computational Study of Inclusion Complexes between Omeprazole Enantiomer with Hydroxypropyl-β-Cyclodextrin

Abstract

Computational study of inclusion complexes between R/S-omeprazole as Proton Pump Inhibitor (PPI) compound with hydroxypropyl-β-cyclodextrin in three of its dimeric structure configurations (head to head, head to tail and tail to tail) has been carried out. All calculations were performed using PM3 quantum semiempirical method. Computational results showed that total binding energy (BE) of R-omeprazole complex is more exothermic than total binding energy of S-omeprazole complex. The calculated binding energy of R-omeprazole complex was -74.65 kcal/mol, while for S-omeprazole complex was -64.09 kcal/mol. This results indicate that R-omeprazole inclusion complex has higher stability compared to S-omeprazole inclusion complex. The value of ΔH, ΔS, and ΔG for R-omeprazole inclusion complex formation were -77.02 kcal/mol, -0.24 cal/mol.K and -2.62 kcal/mol respectively, while the value of ΔH, ΔS, and ΔG for S-omeprazole inclusion complex formation were -66.47 kcal/mol, -0.29 cal/mol.K and 19.29 kcal/mol respectively. These values indicate that the formation of inclusion complexes between R/S-omeprazole with hydroxypropyl-β-cyclodextrin is enthalpy driven process.