Study of the Complexation of Fisetin with Cyclodextrins

In this work, the interaction between fisetin (3,3‘,4‘,7-tetrahydroxyflavone) (Fis) and cyclodextrins (CDs) (α and β) was studied through UV−vis absorption, steady-state fluorescence, induced circular dichroism, and <sup>1</sup>H NMR experiments with dependence on temperature and pH. Some experimental data were compared with quantum-mechanics studies based on the SAM1 (AMPAC) semiempirical model, as well as with the B3LYP and MPW1PW91 functional models from density functional theory using the 6-311G* and 3-21G* basis sets. The spectroscopic measurements show that Fis does not form stable complexes with α-CD. On the other hand, at pH 4.0 and 6.5, the complex Fis−β-CD is formed in a Fis:β-CD 1:1 stoichiometry and an equilibrium constant (<i>K</i>) of 900 ± 100 M<sup>-1</sup>. In basic medium (pH 11.5), <i>K</i> decreases to 240 ± 90 M<sup>-1</sup> because Fis deprotonation leads to its better solubilization in water. Molecular modeling points out that Fis is not totally inserted into the inner cavity of β-CD. The formation of the inclusion complex renders an environment that enhances intramolecular excited state proton transfer. The inclusion complex is formed preferentially via entry of the Fis phenyl group into β-CD.