New Hints on the pH-Driven Tautomeric Equilibria of the Topotecan Anticancer Drug in Aqueous Solutions from an Integrated Spectroscopic and Quantum-Mechanical Approach

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• 作者：Nico Sanna ; Giovanni Chillemi ; Andrea Grandi ; Silvia Castelli ; Alessandro Desideri ; and Vincenzo Barone
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：November 9, 2005
• 年：2005
• 卷：127
• 期：44
• 页码：15429 - 15436
• 全文大小：260K
• 年卷期：v.127,no.44(November 9, 2005)
• ISSN：1520-5126

文摘

The equilibria between the different forms of the topotecan anticancer drug have been studiedat moderately acidic and physiological pH by an integrated computational tool rooted in the density functionaltheory and its time-dependent extension together with the polarizable continuum model. The results allowan unbiased selection between the different possible tautomeric forms and provide invaluable complementsto experimental data. The ultraviolet-visible topotecan spectrum, recorded at moderately acidic pH, isaccurately reproduced only by TD-DFT computations including solvent effects. Comparison of theexperimental and calculated bands of the UV-vis spectrum at physiological pH indicates the presence ofan equilibrium among different forms that is tuned by the microenvironment embedding the drug. Thequantitative agreement between TD-DFT/PCM computations and experiments allows the identification ofunequivocal spectroscopic signatures for different forms of topotecan.