文摘
The interaction of daunomycin with sodium dodecyl sulfate and Triton X-100 micelles was investigated asa model for the hydrophobic contribution to the free energy of DNA intercalation reactions. Measurementsof visible absorbance, fluorescence lifetime, steady-state fluorescence emission intensity, and fluorescenceanisotropy indicate that the anthraquinone ring partitions into the hydrophobic micelle interior. Fluorescencequenching experiments using both steady-state and lifetime measurements demonstrate reduced accessibilityof daunomycin in sodium dodecyl sulfate micelles to the anionic quencher iodide and to the neutral quencheracrylamide. Quenching of daunomycin fluorescence by iodide in Triton X-100 micelles was similar to thatseen with free daunomycin. Studies of the energetics of the interaction of daunomycin with micelles byfluorescence and absorbance titration methods and by isothermal titration calorimetry in the presence of excessmicelles revealed that association with sodium dodecyl sulfate and Triton X-100 micelles is driven by a largenegative 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. Thethermodynamic 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 sulfatemicelles increases nonlinearly with temperature, indicating a positive (and temperature dependent) heat capacitychange. 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 thedrug alters micelle size or imposes order on the hydrocarbon interior of the micelle.