Theoretical Study on Intermolecular Interactions in Complexes of Cyclodextrins with Bile Acids: DFT and Ab Initio Fragment Molecular Orbital Calculations

Inclusion complexes composed of cyclodextrin (CD) and bile acids have potential applications in drug delivery systems and chiral separation technology. In the present study, intermolecular interactions in 1:1 complexes of α-, β-, and γ-CDs with cholic acid (CA) or deoxycholic acid were analyzed both in the gas phase and in aqueous phase with density functional theory (B97-D and M06-2X) with the standard 6-31G(d) basis set together with the B3LYP functional for comparison. The association energies depend on the distance between CD and the guest as well as on the relative position and orientation of the guest in the cavity. The most stable binding mode for each complex is consistent with that proposed by NMR experiments. A pair interaction energy decomposition analysis based on ab initio fragment molecular orbital calculations was performed at the FMO-MP2/cc-pVDZ level of theory. It reveals that the β-CD/CA has more negative host–guest interaction energy than the γ-CD/CA and that dispersion and electrostatic interactions contribute comparably to the stabilization of the complexes. Several hydrogen bonds between CD and the guest also stabilize the complex.