Molecular dynamics of β-CD in water/co-solvent mixtures

Molecular dynamics (MD) simulations on beta-cyclodextrin (beta-CD) in water, ethanol (EtOH), methanol (MeOH) and mixtures of these solvents have been carried out at 300 K over a time period of 15 ns using the AMBER force field. The hydrated X-ray crystallographic structure has four water molecules inside the cavity, defined by a more precise boundary for the beta-CD cavity. From the simulations, 2-4 encapsulated water molecules are most probably found. In an ethanol co-solvent system, the beta-CD cavity is occupied with one ethanol molecule located in two discrete sites: below and above the O4(n) plane, which is in agreement with experimental results. In all systems, the average values of tilt angles of the obtained structures are higher than the tilt angles of the X-ray structures. The investigations of the alcohol orientations in co-solvent mixtures reveal the hydrophobic environment of the cavity and the hydrophilic atmosphere at both rims of beta-CD.