The Curious Case of Aqueous Warfarin: Structural Isomers or Distinct Excited States?

Sushil S Sakpal, Deborin Ghosh, Meghna A Manae, Anirban Hazra, Sayan Bagchi

The journal of physical chemistry. B 2021 Mar 25

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Warfarin is a potent anti-coagulant drug and is on the World Health Organization's List of Essential Medicines. Additionally, it displays fluorescence enhancement upon binding to human serum albumin, making warfarin a prototype fluorescent probe in biology. Despite its biological significance, the current structural assignment of warfarin in aqueous solution is based on indirect evidence in organic solvents. Warfarin is known to exist in different isomeric forms-open-chain, hemiketal, and anionic forms-based on the solvent and pH. Moreover, warfarin displays a dual absorption feature in several solvents, which has been employed to study the ring-chain isomerism between its open-chain and hemiketal isomers. In this study, our pH-dependent experiments on warfarin and structurally constrained warfarin derivatives in aqueous solution demonstrate that the structural assignment of warfarin solely on the basis of its absorption spectrum is erroneous. Using a combination of steady-state and time-resolved spectroscopic experiments, along with quantum chemical calculations, we assign the observed dual absorption to two distinct π → π* transitions in the 4-hydroxycoumarin moiety of warfarin. Furthermore, we unambiguously identify the isomeric form of warfarin that binds to human serum albumin in aqueous buffer.

Citation

Sushil S Sakpal, Deborin Ghosh, Meghna A Manae, Anirban Hazra, Sayan Bagchi. The Curious Case of Aqueous Warfarin: Structural Isomers or Distinct Excited States? The journal of physical chemistry. B. 2021 Mar 25;125(11):2871-2878