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

Area of Science:

• Photochemistry
• Supramolecular Chemistry
• Analytical Chemistry

Background:

• Warfarin (W) is an anticoagulant drug with distinct open and cyclic protonated isomers.
• Cyclodextrins are cyclic oligosaccharides known for their ability to form inclusion complexes with various molecules.
• Understanding the interactions between warfarin and cyclodextrins is crucial for drug delivery and formulation.

Purpose of the Study:

• To investigate the excited-state lifetimes and binding interactions of warfarin isomers with methyl-β-cyclodextrins (Me-β-CD).
• To elucidate the influence of Me-β-CD on the photophysical properties of warfarin.
• To determine the binding constants and preferential binding modes of warfarin isomers within the Me-β-CD cavity.

Main Methods:

• Time-resolved fluorescence spectroscopy was employed to measure excited-state lifetimes.
• UV-visible absorption spectroscopy was used to determine binding constants and monitor complex formation.
• Selective excitation of warfarin isomers was achieved using specific laser emitting diodes (LEDs).

Main Results:

• Me-β-CD preferentially binds the open protonated form of warfarin, red-shifting its absorption and extending its excited-state lifetime.
• Binding of warfarin to Me-β-CD decreases its emission quantum yield and radiative rate constants, suggesting hydrogen-bonded complex formation.
• The cyclic form of warfarin showed no significant change in excited-state lifetime upon interaction with Me-β-CD.
• Me-β-CD enhances the excited-state lifetime and quantum yield of the deprotonated warfarin form (W⁻), likely due to increased rigidity within the cavity.
• Warfarin's open isomer is more acidic in both ground and excited states, and cyclodextrin derivatives favor binding to open isomers.

Conclusions:

• Me-β-CD forms stable inclusion complexes with warfarin, with a preference for the open protonated isomer.
• The photophysical properties of warfarin are significantly altered upon complexation, providing insights into host-guest interactions.
• The study highlights the potential of cyclodextrins in modulating the properties of warfarin for pharmaceutical applications.