The spectrophysics of warfarin: Implications for protein binding
The spectrophysics of warfarin: Implications for protein binding
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DOI：
10.1021/jp072505i
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发表时间：
2007-09-06
影响因子：
3.3
通讯作者：
Nicholls, Ian A.
中科院分区：
文献类型：
--
作者：
Karlsson, Bjorn C. G.;Rosengren, Annika M.;Nicholls, Ian A.
结合基于b3lyp的理论处理方法，利用吸收、H-1 NMR、稳态和时间分辨荧光光谱研究了抗凝血药物华法林的异构体在各种溶剂和溶剂混合物中的光物理行为。观察到复杂的吸收模式，表明华法林在不同溶剂中存在不同的异构体。在碱性水溶液中，华法林以去质子化开侧形式为主，在320 nm处的吸收光谱中只观察到一个so - s1单重态跃迁。理论密度函数计算（B3LYP）对华法林9种异构体的几何形状进行了优化，并预测了它们各自的8个最低单重态和3个最低三重态激发能级。在非极性和极性有机溶剂中对华法林异构体的荧光激发和发射光谱进行了检测，发现华法林在2-丙醇、乙醇和乙腈中存在去质子化的开侧链形式。时间分辨荧光实验显示，在所研究的所有溶剂中，衰减时间常数tau(1)都很短，而在极性更高的环境中，第二长的衰减时间常数tau(2)明显在0.5至1.6 ns之间变化，具体取决于溶剂极性。荧光寿命的数目和长度随溶剂环境的变化为检测华法林蛋白结合提供了一种工具。已经进行了华法林与人血清白蛋白（HSA）结合的研究，观察到不同的结合模式，表明与阴离子选择性Sudlow I结合，其次是低亲和力的相互作用模式。
The photophysical behavior of the isomers of the anticoagulant drug warfarin in various solvents and solvent mixtures was investigated using absorption, H-1 NMR, and steady-state and time-resolved fluorescence spectroscopies in conjunction with B3LYP-based theoretical treatments. Complex absorption patterns were observed, indicative of the presence of different isomers of warfarin in the various solvents studied. In alkaline aqueous solution, the deprotonated open side form of warfarin is highly dominant and only one SO-S 1 singlet transition could be observed in the absorption spectrum centered at 320 nm. These observations were supported by theoretical density functional calculations (B3LYP) in which the geometries of nine isomers of warfarin were optimized and their respective eight lowest singlet and three lowest triplet excitation energy levels were predicted. Examination of the fluorescence excitation and emission spectra of the isomers in nonpolar and polar 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, tau(1), in all solvents studied while in more polar environments a second longer one, tau(2), was evident varying between 0.5 and 1.6 ns depending on solvent polarity. The variation of number and length of fluorescence lifetimes as a function of solvent environment has provided a tool for examining warfarin protein binding. Studies on the binding of warfarin to human serum albumin (HSA) have been undertaken, and different modes of binding were observed which are indicative of binding to the anion-selective Sudlow I and, second, a lower affinity mode of interaction.