Spectroscopy and dynamics of topotecan anti-cancer drug comprised within cyclodextrins

We report on photophysical studies of the interaction between an anti-cancer drug, topotecan (TPT), in aqueous buffered (pH = 7.23) solutions of three different β-CDs, native and methylated ones (DM-β-CD and TM-β-CD). We used UV–visible absorption and emission (steady-state and time-resolved) spectroscopy to follow the dynamical and structural changes due to the hydrophobicity and confinement effect of the CDs on both the ground- and excited-state behaviour of TPT. Both 1H NMR and absorption experiments give evidences for the encapsulation of the enol form of TPT as the most favourable one. In addition, the host–guest interaction becomes stronger as the hydrophobic character provided by the methylated groups of the host increases. The equilibrium constants of the formed TPT:β-CD, TPT:DM-β-CD, and TPT:TM-β-CD 1:1 complexes are K296 K (104 M−1) = 0.88, 2.4, and 3.7, respectively. Semiempirical (PM3) calclulations suggest that the docking of TPT is through its quinoline moiety, in agreement with the 1H NMR assignment. We found that the hydrophobic environment provided by the CD cavity influences the deactivation channels of the emitting species by modifying the rate of the non-radiative processes upon encapsulation. The excited-state proton-transfer (ESPT) rate constants are affected by the degree of protection of the guest inside the host. Rotational times from picosecond anisotropy measurements (φ = 156, 169, and 178 ps for TPT, TPT:β-CD, and TPT:TM-β-CD, respectively) indicates that the drug is still able to rotate inside the CD. These findings are relevant to drug–host interactions and proton-transfer reaction dynamics in supramolecular systems for structurally related drugs, and should contribute to the development of drug delivery field.

The behaviour of topotecan (TPT), a potent anticancer drug, in presence of different β-cyclodextrins (β-CD), native and methylated ones, is investigated by UV–visible absorption, emission (steady-state and time-resolved), and 1H NMR spectroscopies, in addition to PM3 calculations. The results reveal that the encapsulated neutral (enol) form of TPT is the most favourable one. The host–guest interaction becomes stronger as the hydrophobic character of the CD gate increases. The excited-state proton-transfer (ESPT) rate constants are affected by the degree of protection of the guest inside the host.Figure optionsDownload as PowerPoint slide