The Spectrophysics of Warfarin: Implications for Protein Binding
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- 作者：Bjö ; rn C. G. Karlsson ; Annika M. Rosengren ; Per Ola Andersson ; Ian A. Nicholls
- 刊名：Journal of Physical Chemistry B
- 出版年：2007
- 出版时间：September 6, 2007
- 年：2007
- 卷：111
- 期：35
- 页码：10520 - 10528
- 全文大小：441K
- 年卷期：v.111,no.35(September 6, 2007)
- ISSN：1520-5207
文摘
The photophysical behavior of the isomers of the anticoagulant drug warfarin in various solvents and solventmixtures was investigated using absorption, 1H NMR, and steady-state and time-resolved fluorescencespectroscopies in conjunction with B3LYP-based theoretical treatments. Complex absorption patterns wereobserved, indicative of the presence of different isomers of warfarin in the various solvents studied. In alkalineaqueous solution, the deprotonated open side form of warfarin is highly dominant and only one S0
S1 singlettransition could be observed in the absorption spectrum centered at 320 nm. These observations were supportedby theoretical density functional calculations (B3LYP) in which the geometries of nine isomers of warfarinwere optimized and their respective eight lowest singlet and three lowest triplet excitation energy levels werepredicted. Examination of the fluorescence excitation and emission spectra of the isomers in nonpolar andpolar organic solvents showed the presence of the deprotonated open side chain form of warfarin in 2-propanol,ethanol, and acetonitrile. Time-resolved fluorescence experiments revealed a short decay time constant, 
1, inall solvents studied while in more polar environments a second longer one, 2, was evident varying between0.5 and 1.6 ns depending on solvent polarity. The variation of number and length of fluorescence lifetimesas a function of solvent environment has provided a tool for examining warfarin protein binding. Studies onthe binding of warfarin to human serum albumin (HSA) have been undertaken, and different modes of bindingwere observed which are indicative of binding to the anion-selective Sudlow I and, second, a lower affinitymode of interaction.
S1 singlettransition could be observed in the absorption spectrum centered at 320 nm. These observations were supportedby theoretical density functional calculations (B3LYP) in which the geometries of nine isomers of warfarinwere optimized and their respective eight lowest singlet and three lowest triplet excitation energy levels werepredicted. Examination of the fluorescence excitation and emission spectra of the isomers in nonpolar andpolar organic solvents showed the presence of the deprotonated open side chain form of warfarin in 2-propanol,ethanol, and acetonitrile. Time-resolved fluorescence experiments revealed a short decay time constant, 1, inall solvents studied while in more polar environments a second longer one, 2, was evident varying between0.5 and 1.6 ns depending on solvent polarity. The variation of number and length of fluorescence lifetimesas a function of solvent environment has provided a tool for examining warfarin protein binding. Studies onthe binding of warfarin to human serum albumin (HSA) have been undertaken, and different modes of bindingwere observed which are indicative of binding to the anion-selective Sudlow I and, second, a lower affinitymode of interaction.