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

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• 作者：Maria Rosaria di Nunzio ; YiLun Wang ; Abderrazzak Douhal
• 关键词：Anticancer drug ; Topotecan ; Cyclodextrin ; Spectroscopy ; Inclusion complexes ; Proton-transfer dynamics
• 刊名：Journal of Photochemistry and Photobiology A: Chemistry
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：266
• 期：Complete
• 页码：12-21
• 全文大小：1703 K

文摘

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 ¦Â-CDs, native and methylated ones (DM-¦Â-CD and TM-¦Â-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:¦Â-CD, TPT:DM-¦Â-CD, and TPT:TM-¦Â-CD 1:1 complexes are K_296 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 (¦Õ = 156, 169, and 178 ps for TPT, TPT:¦Â-CD, and TPT:TM-¦Â-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.