Kinetics and thermodynamics of the formation of inclusion complexes between cyclodextrins and DNA-intercalating agents. Inclusion of ellipticine in γ-cyclodextrin

Abstract

Ellipticine (E) seems to be included in two steps by two γ-cyclodextrin molecules. The first inclusion is detected by changes in the absorbance spectrum of ellipticine with added cyclodextrin. It occurs from the pyridine side of the molecule to form E–CD, the first inclusion complex, with a dissociation constant K₁= 9.80 × 10^–5 mol dm^–3 and a T-jump-measured second-order rate constant k₁= 3.6 × 10⁶ dm³ mol^–1 s^–1. E–CD is then included by another γ-cyclodextrin molecule to form E–CD₂, the second inclusion complex. As evidenced by changes in the absorbance and fluorescence spectra of E, this second inclusion occurs from the indole side of the molecule with a dissociation constant K₂= 1.85 × 10^–1 mol dm^–3 and with a second-order rate constant k₂ > 10⁷ dm^–3 mol^–1 s^–1. These results may be of interest in chemotherapy based on the use of planar DNA-intercalating agents.