Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV-visible absorption spectroscopy, and the values of binding constants (2.9 × 10³ M^-1 and 4.2 × 10² M^-1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (Ф_F). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (k_r), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and Ф_F of the drug deprotonated form (W^-). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pK_a values extracted from the variations of the UV-visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pK_a values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.