Cyclodextrin-assisted photostabilization of 5-fluorouracil: a combined kinetic and computational investigation.

The photostabilization of 5-fluorouracil (5-FU) has been carried out in the pH range of 2.0-12.0 using cyclodextrins (α-, β-, γ-) as a complexing agent. The inclusion complex formation between 5-FU and CDs has been evaluated using conductometry, FTIR spectroscopy, NMR spectroscopy, differential scanning calorimetry (DSC), and molecular docking simulations. The loss of absorbance at 266 nm for 5-FU in the presence of CDs indicates its photodegradation. The entrapment of 5-FU in α-, β-, and γ-CDs ranges from 22.0-58.0, 30.0-64.0, and 42.0-77.0%, respectively, indicating the formation of inclusion complexes of CDs with 5-FU. The values of Stern-Volmer fluorescence quenching constants and binding constants for α-, β- and γ-CDs are 1.10, 1.69, 3.06 × 10 L mol and 2.89, 3.11, 3.62 10 L mol, respectively. The apparent first-order rate constants ( ) for the photodegradation of 5-FU in the presence of α-, β-, and γ-CDs are 1.75-5.12, 1.21-4.89, and 0.85-4.69 × 10, min, respectively. The photochemical interaction ( ) of 5-FU with α-, β-, and γ-CDs ranges from 0.25-0.49, 0.63-1.47, and 0.79-2.14 M min in the pH range 2.0-12.0. The mode of photochemical interaction of 5-FU and CDs and the photostabilization of 5-FU is described based on H-atom abstraction by 5-FU from CD and radical-radical recombination. The computational analysis complemented the experimental findings, showing a significant second-order donor-acceptor interaction, particularly LP → π*, between the hydroxyl groups of γ-CD and the carbonyl groups of 5-FU. The natural population analysis further revealed a shift in electron density from γ-CD to 5-FU, indicating a protective charge-transfer mechanism that contributes to the photostabilization of 5-FU.