Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry

Abstract

Non-covalent inclusion complexes formed between an anti-inflammatory drug, oleanolic acid (OA), and alpha-, beta- and gamma-cyclodextrins (CDs) were investigated by means of solubility studies and electrospray ionization tandem mass spectrometry (ESI-MS(n)). The order of calculated association constants (K(1 : 1)) of complexes between OA and different CDs in solution is in good agreement with the order of their relative peak intensities and the relative CID energies of the complexes under the same ESI-MS(n) conditions. These results indicate a direct correlation between the behaviors of solution- and gas-phase complexes. ESI-MS can thus be used to evaluate solution-phase non-covalent complexes successfully. The experimental results show that the most stable 1 : 1 inclusion complexes between three CDs and OA can be formed, but 2 : 1 CD-OA complexes can be formed with beta- and gamma-CDs. Multi-component complexes of alpha-CD-OA-beta-CD (1 : 1 : 1), alpha-CD-OA-gamma-CD (1 : 1 : 1) and beta-CD-OA-gamma-CD (1 : 1 : 1) were found in equimolar CD mixtures with excess OA. The formation of 2 : 1 and multi-component 1 : 1 : 1 non-covalent CD-OA complexes indicates that beta- and gamma-CD are able to form sandwich-type inclusion non-covalent complexes with OA. The above results can be partly supported by the relative sizes of OA and CD cavities by molecular modeling calculations. All the complexes allow the detection of gaseous deprotonated CD-OA complexes in the negative ion mode at high abundances. The relative stabilities of the CDs-OA inclusion complexes in the gas phase can be evaluated from the relative CID energies in the ion trap (alpha-CD-OA < beta-CD-OA < gamma-CD-OA) in the negative ion mode.