Dignam John David, Qu Xiaogang, Ren Jinsong, Chaires Jonathan B
Department of Biochemistry and Cancer Biology, Block Health Science Building, University of Toledo College of Medicine, 3035 Arlington Avenue, Toledo, Ohio 43614-5804, USA.
J Phys Chem B. 2007 Oct 4;111(39):11576-84. doi: 10.1021/jp066877n. Epub 2007 Sep 11.
The interaction of daunomycin with sodium dodecyl sulfate and Triton X-100 micelles was investigated as a model for the hydrophobic contribution to the free energy of DNA intercalation reactions. Measurements of visible absorbance, fluorescence lifetime, steady-state fluorescence emission intensity, and fluorescence anisotropy indicate that the anthraquinone ring partitions into the hydrophobic micelle interior. Fluorescence quenching experiments using both steady-state and lifetime measurements demonstrate reduced accessibility of daunomycin in sodium dodecyl sulfate micelles to the anionic quencher iodide and to the neutral quencher acrylamide. Quenching of daunomycin fluorescence by iodide in Triton X-100 micelles was similar to that seen with free daunomycin. Studies of the energetics of the interaction of daunomycin with micelles by fluorescence and absorbance titration methods and by isothermal titration calorimetry in the presence of excess micelles revealed that association with sodium dodecyl sulfate and Triton X-100 micelles is driven by a large negative enthalpy. Association of the drug with both types of micelles also has a favorable entropic contribution, which is larger in magnitude for Triton X-100 micelles than for sodium dodecyl sulfate micelles. The thermodynamic profile for the interaction of daunomycin with both types of micelles is characteristic of the "nonclassical" hydrophobic effect. The enthalpy for the interaction of daunomycin with sodium dodecyl sulfate micelles increases nonlinearly with temperature, indicating a positive (and temperature dependent) heat capacity change. The binding isotherm for daunomycin association with sodium dodecyl sulfate micelles was cooperative, with a Hill coefficient of 1.6. The cooperative behavior and the positive heat capacity change suggest that the drug alters micelle size or imposes order on the hydrocarbon interior of the micelle.
研究了柔红霉素与十二烷基硫酸钠和 Triton X - 100 胶束的相互作用，以此作为疏水作用对 DNA 嵌入反应自由能贡献的模型。可见吸光度、荧光寿命、稳态荧光发射强度和荧光各向异性的测量结果表明，蒽醌环进入了疏水胶束内部。使用稳态和寿命测量的荧光猝灭实验表明，在十二烷基硫酸钠胶束中，柔红霉素对阴离子猝灭剂碘化物和中性猝灭剂丙烯酰胺的可及性降低。在 Triton X - 100 胶束中，碘化物对柔红霉素荧光的猝灭与游离柔红霉素的情况相似。通过荧光和吸光度滴定法以及在过量胶束存在下的等温滴定量热法研究柔红霉素与胶束相互作用的能量学，结果表明与十二烷基硫酸钠和 Triton X - 100 胶束的缔合由很大的负焓驱动。药物与这两种胶束的缔合也有有利的熵贡献，Triton X - 100 胶束的熵贡献幅度大于十二烷基硫酸钠胶束。柔红霉素与这两种胶束相互作用的热力学特征是“非经典”疏水效应。柔红霉素与十二烷基硫酸钠胶束相互作用的焓随温度非线性增加，表明有正的（且与温度相关的）热容变化。柔红霉素与十二烷基硫酸钠胶束缔合的结合等温线是协同的，希尔系数为 1.6。协同行为和正的热容变化表明药物改变了胶束大小或使胶束的烃类内部有序化。
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