Theoretical study on interactions of β-cyclodextrin with Helicobacter pylori eradicating agent (TG44)

The inclusion complex of β-cyclodextrin (β-CD) and 4-methylbenzyl-4'-[trans-4- (guanidinomethyl)cylohexylcarbonyloxy]-biphenyl-4-carboxlylate monohydrochloride (TG44) had been investigated by using densify functional theory (DFT) and PM3 semiempirical method. The results indicate that the β-CD includes predominantly the biphenyl moiety of TG44, and the inclusion complex formed by TG44 entering into the cavity of β-CD from its narrow side (the primary hydroxyl group side) is more stable than that formed by TG44 entering into the cavity of β-CD from its wide side (the secondary hydroxyl group side). The negative enthalpy changes calculated from the statistical thermodynamic calculations at 1 atm and 298.15 K suggest that the inclusion complexes are favored enthalpy-driven processes. The molecular modeling results are in good agreement with the experiment for 2D (1)H-(13)C H HETCOR spectroscopic and H-NMR spectroscopic observations.