Multidisciplinary investigation of atypical inclusion complexes of beta-cyclodextrin and a phospholipase-A2 inhibitor

BMS-188184, an anthracene derivative, has been found to form at least two complexes with beta-cyclodextrin. The association/dissociation kinetics of the two complexes were extremely slow, with one complex requiring approximately 24 h, and the other complex requiring more than 8 weeks, to reach equilibrium. The stability constants of the two complexes were estimated at approximately 11,000 and 39,000 M(-1) under nonequilibrium conditions. The slow rates of dissociation allowed the complexes and the unbound BMS-188184 to be separated using high-performance liquid chromatography. Exact mass liquid chromatography/mass spectrometry, tandem mass spectrometry, and nuclear magnetic resonance techniques were used to characterize the stoichiometry of both complexes as 1:1. Because of the ability of the complexes to survive high-performance liquid chromatography analysis, their slow reaction rates, and 1:1 stoichiometry, the complexes were tentatively characterized as [2]-rotaxanes. The available data suggest that the two complexes are conformational isomers.