Date of Award
Master of Science (MS)
Na’il Saleh Ibrahim
Mohammed A. Meetani
In this work, the photophysical properties of the fluorescent anticoagulant drug warfarin (W) were examined in water and inside methyl-β-cyclodextrins (Me-β- CD) through absorption and time-resolved fluorescence measurements at pH 3 and 9 and upon the selective excitation of different isomers of warfarin at 280 and 320 nm. 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 (ՓF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), 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 ՓF of the drug deprotonated form (W-). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa 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 pKa 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.
Al-Dubaili, Naji Saleh Ahmed, "Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced By Cyclodextrin: Time-Resolved Fluoresence Study" (2018). Chemistry Theses. 5.