Study of the Complexation of Fisetin with Cyclodextrins

Abstract

In this work, the interaction between fisetin (3,3',4',7-tetrahydroxyflavone) (Fis) and cyclodextrins (CDs) (alpha and beta) was studied through UV-vis absorption, steady-state fluorescence, induced circular dichroism, and (1)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 alpha-CD. On the other hand, at pH 4.0 and 6.5, the complex Fis-beta-CD is formed in a Fis:beta-CD 1:1 stoichiometry and an equilibrium constant (K) of 900 +/- 100 M(-1). In basic medium (pH 11.5), K decreases to 240 +/- 90 M(-1) 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 beta-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 beta-CD.

Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin

“…One study found that fisetin could only form a stable complex with β-cyclodextrin, but not with the α-cyclodextrin [11]. Complexation of fisetin with another type of cyclodextrin (γ-cyclodextrin) was also undertaken in order to understand the behaviour of fisetin in the nano-cavity, and confirmed the suitability of the nano-vehicle for parenteral administration of fisetin [12].…”

Photophysics of Caffeic, Ferulic and Sinapic Acids with α- and β-Cyclodextrins: Spectral and Molecular Modeling Studies

“…Hence, the ICT emission intensity should be almost unaltered because the energy barrier to form ICT state not only depends upon rotation of OH/OCH 3 but also on hydrogen bonding between the guest and the water. The energy barrier for formation of ICT state does not change as long as hydrogen bonding is still possible [33][34][35] between HCA and water molecules. So the huge enhancement of the ICT state suggests that among these two types of orientations of HCA molecule inside the CD cavity results in a huge observed enhancement of the LW band with red band shift as it is emitted from the most nonpolar state of HCA and a small enhancement of the SW state without any spectral shift.…”

“…So the SW band remains unaffected. When two π-moieties of the HCA are not in orthogonal position inside the CD cavity it causes an enhancement of radiative transition probability [33][34][35] of the ICT state and an increase in the ICT band. But the hydrogen bond formation of the C=O group of HCA with water molecules makes the ICT state more stable by lowering its energy level resulting in an extra red shift of the low energy (ICT) band.…”

Fluorescence Studies of the Hydrogen Bonding of Excited‐State Molecules within Supramolecular Host–Guest Inclusion Complexes

“…They attributed this rate decrease to the existence of a network of hydrogen-bonded bridging waters separating the donor and acceptor in these complexes; this network would need to undergo significant rearrangement for ESPT to occur. In addition to such intermolecular proton transfer to solvent, excited-state intramolecular proton transfer (ESIPT) can also occur for specific molecules, and this process has also been extensively studied within CD cavities [91][92][93][94][95]. Once again, inclusion into a CD cavity disrupts the hydrogen bonding of the excited guest with the solvent; however, in this case, disruption of solvent hydrogen bonding actually favours intramolecular hydrogen bonding, and hence the rate of ESIPT can be enhanced upon CD inclusion [91][92][93][94].…”

“…In addition to such intermolecular proton transfer to solvent, excited-state intramolecular proton transfer (ESIPT) can also occur for specific molecules, and this process has also been extensively studied within CD cavities [91][92][93][94][95]. Once again, inclusion into a CD cavity disrupts the hydrogen bonding of the excited guest with the solvent; however, in this case, disruption of solvent hydrogen bonding actually favours intramolecular hydrogen bonding, and hence the rate of ESIPT can be enhanced upon CD inclusion [91][92][93][94]. In other cases, direct hydrogen bonding between the guest and CD hydroxyls reduces intramolecular hydrogen bonding, resulting in a decreased rate of ESIPT [95].…”