Density functional calculations on meloxicam–β-cyclodextrin inclusion complexes

The geometries of the cyclodextrin (CD) inclusion complexes with various tautomeric forms of meloxicam in gas phase were determined by DFT calculation (B3LYP/6-31G (d,p)). The interaction energies were estimated including basis set superposition error (BSSE) correction. Two orientations of the meloxicam guest were considered: the benzene ring located near the narrow rim and at the wider rim of the β-cyclodextrin, respectively. The calculations show that in all cases the molecules are located inside the CD cavity. The preferred complexation orientation is that one, in which the benzene ring of meloxicam is located near the wider rim with the secondary hydroxyl groups of the CD. The stabilization energies for the encapsulation of the meloxicam guest molecules show an overall affinity ranking for the meloxicam guest molecule in the following order: anionic (deprotonated) form > zwitterionic form ∼ enolic form > cationic (protonated) form. A comparison of the enolic and zwitterionic neutral forms shows, that the zwitterionic structure is better stabilized upon complexation due to the geometry of two extra hydrogen bonds between host and guest.