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

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